HCDI4 UPDATES AND ADDITIONS Dec' 16

UPDATES AND ADDITIONS
for
Herbal Contraindications & Drug Interactions
plus Herbal Adjuncts with Medicines
FOURTH EDITION
by Francis Brinker, N.D.
Copyright 2016
All rights reserved.
Last updated: December 6, 2016
NEW FEATURE: An index for the Updates and Additions is now included at the end.
This document and its contents may not be reproduced for distribution or sale in any form.
NOTICE
Information provided in the book or these updates and additions is not intended as
recommendations for self treatment or to substitute for instructions provided by one’s own doctor
or health care provider. Combining herbal use with medications should only be done after
consultation with a knowledgeable physician. Preliminary research data on potentially beneficial
combinations of herbals and drugs is provided to educate pharmacists and physicians and
encourage further clinical research. Information provided in the book and in these updates is not
intended as recommending self treatment or to replace instructions provided by one’s own doctor
or health care provider.
Disclaimer
The author and publisher, in attempting to prepare the book with the utmost accuracy from thousands of
sources, make no guarantees of any kind on the reliability of the references used and assume no
responsibility for any errors or omissions in citing these references. They assume no liability for any
damages in connection with the information contained in the book or in the updates and additions or
arising from application of the information to oneself or others.
Where the bracketed phrase [Note CORRECTION:] appears before numbers or information in ALL
CAPS in these Updates and Additions, it denotes an error found in early printings of the book (those prior
to 2013). The corrections were made in ongoing printings and the Kindle version (2013) of the book. It is
recommended that if the noted corrections have not been made in the book in your possession, that you
make the appropriate changes directly in your hard copy and/or insert a copy of the compilation of all
CORRECTIONS that is given before the Index at the end of these Updates after the References.
KEYS TO INTERPRETING THE CONTENT IN THE BOOK AND AT THIS SITE

The following terms are used to describe the different means of determining botanical effects.
[At www.eclecticherb.com/emp/herb-contraindications-drug-interactions/ a free, printable, tri-fold
bookmark with the following designations is available in pdf format.]
Where contradicting data exists for a particular item in any category, this is noted by an indentation, and
the sentence will begin with the capitalized word, 'HOWEVER'.
1
Contraindications
I. clinical – (empirical observations, human research, or case reports)
II. pre-clinical – (indirect in vitro or in vivo laboratory studies (speculative outcomes for humans)
Drug Interactions
Ia. human studies – published research done on healthy individuals
human clinical studies – published research from therapeutic trials on patients being treated for a
condition
Ib. empirical – traditional knowledge or consensus based on experience from extensive use
human case reports – published individual responses to using herbal products
human case series – published responses from several patients using a preparation of the same
herb
II. in animals (types listed) – laboratory tests using live animals (in vivo) and various modes of
administering the herb or herbal component(s)
III. ex vivo –laboratory interaction finding on cells, tissue, or organs from animals or humans who
were administered the herbal agent (as contrasted to in vivo when studies are
done on the living organisms themselves)
in vitro –laboratory interaction finding with cell or tissue samples from animals or humans
speculative – using pharmacological evidence from in vitro research, animal studies, or human
studies to infer probable or potential interactions or effects in humans
IV. [dubious interactions], as shown in brackets with the drugs underlined rather than in bold type,
are based on preliminary findings, speculation, inaccurate information, and/or false assumptions
that have been contradicted by established evidence.
Complementary Adjuncts
Conditions, symptoms, or markers impacted or the drug adverse effects reduced are designated by bold
underline.
Ia. human clinical trials
Ib. case reports, empirical observations
IIa. in vivo animal studies
IIb. in vitro laboratory research
Abbreviations for the various modes of administration are used as follows:

IM (intramuscular) – injected into a large skeletal muscle
IP (intraperitoneal) – injected into the peritoneal cavity
IV (intravenous) – injected into a vein
PO (per os) – by mouth; orally or through a feeding tube; b.i.d. = 2x/day, t.i.d. = 3x/day
SC (subcutaneous) – injected under the skin
* An asterisk in front of an herb’s scientific name denotes toxic effects from over-consumption of that
herb or a major active component.
ADDITIONAL INFORMATION IS AVAILABLE IN THESE UPDATES AND ADDITIONS FOR THE

FOLLOWING LISTED HERBS AND APPENDICES, AS DESIGNATED:
+ denotes new contraindication(s), interaction(s), and/or complementary adjuncts not previously listed in
the book for the herb
^ denotes new herb with contraindication(s), interaction(s) and/or complementary adjuncts in body of text
or an entirely new appendix section
If none of the above are present in the list below, further elaborations have been made to information
already included in the book.
2
HERBAL AGENTS
The following list are those herbs that are new (^), or have new categories added (+), or have information
updated.
Aloe
American ginseng +
Amla ^
Anise +
Arjuna +
Arnica +
Ashwagandha +
Asian ginseng +
Astragalus +
Barberry +
Bilberry +
Bitter melon
Bitter orange
Black cohosh
Black cumin +
Black pepper +
Black raspberry ^
Boldo +
Borage +
Burdock +
Calamus +
Cannabis +
Cassia +
Cat's claw +
Cayenne +
Celandine
Chaga ^
Chamomile
Chili ^
Chinese hibiscus [formerly Hibiscus]
Chinese rhubarb +
Chinese skullcap +
Chokeberry +
Cinchona
Cinnamon +
Clove +
Cocoa +
Cola +
Coptis +
Corn silk ^
Cranberry
Crucifers +
Dan shen +
Dog rose +
Dong Quai +
Echinacea angustifolia
Echinacea pallida +
Echinacea purpurea +
3
English plantain +
Eucalyptus +
Evening primrose +
Fenugreek +
Fo-ti
Frankincense +
French maritime pine +
Garlic +
Ginger +
Ginkgo
Goldenseal +
Grapefruit +
Guarana +
Guggul +
Hawthorn +
Hibiscus ^
Hops +
Horse chestnut +
Jujube +
Kava
Kudzu +
Kutaki +
Larch ^
Licorice +
Long pepper +
Lycium +
Maca
Maitake +
Milk thistle +
Oat
Olive +
Oregon grape +
Passion flower
Pau d'Arco +
Pelargonium ^
Peppermint +
Pomegranate +
Prickly pear
Psyllium
Quassia (Surinam) +
Raspberry +
Roman chamomile
Saffron +
Sage +
Sanch ginseng ^
Saw palmetto +
Schisandra +
Shiitake ^
Silk tree +
Southern schizandra ^
Soy +
4
St. John's wort
Stinging nettle
Sweet annie +
Sweet cherry ^
Tart cherry ^
Tea +
Tea tree +
Thunder god vine
Tibetan rhodiola ^
Tulsi ^
Turmeric +
Valerian +
Wild yam +
Yohimbe
APPENDICES
The following are entirely new sections and subsections.
A.8 Bioactivations of Phytochemical Procarcinogens and Potential Toxins ^
A.8.1 Bioactivations by Cytochrome P450 Isozymes (CYPs) and Sulfotransferases (STs) ^
B.7.1.d Influence on Constitutive Androstane Receptor (CAR)

B.7.3.f Influence on Activity of Estrogen Sulfotransferases (SULT1E1)
B.7.4.i 11beta-Hydroxysteroid Dehydrogenase type 1 Conversion of Cortisone to Cortisol ^
B.7.4.j Sterol 27-Hydroxylase (CYP27A1) Conversion of Cholesterol to Bile Acids
and Bioactivation of Vitamin D3
^
E.5.9 Potential Herbal Prevention of Dermal Photocarcinogenesis ^
E.5.10 Herbal Prevention of Acute UV-induced Erythema ^
E.5.11 Herbal Protection Against Radioiodine Therapy Adverse Effects ^
E.6.11 Botanicals reducing adverse effects caused by antimicrobial agents ^
The following are those sections and subsections for which new information has been added.
B.1 Modifying Intestinal Absorption of Medicines and Phase III Metabolism
B.1.1 Slowed and/or Reduced Absorption by Herbal Components
B.1.2 Enhancement of Absorption
B.4 Modifying Blood Sugar In Diabetics
B.4.1 Hypoglycemic and/or Antihyperglycemic Herbals
B.4.2 Antihyperglycemic Botanicals Enhancing Oral Hypoglycemic Drugs in Humans
B.5 Modifying the Effects of Anticoagulants
B.5.1 Increasing Potential for Hemorrhage
B.5.2 Increasing Potential for Coagulation
B.7 Modifying Enzyme Activities in Metabolic Conversions
B.7.1 Unspecified Influences of Herbal Agents on Substrate Pharmacokinetics
B.7.2 Influences of Herbal Agents in Phase I on Specific Cytochrome P450 Isozymes
B.7.3 Specific Enzyme Influences of Herbal Agents on Phase II Conjugation
B.7.4 Specific Enzyme Influences of Herbal Agents on Steroid Metabolism
C.1 During Pregnancy

C.1.1 Herbals That May Impact the Uterus or Fetal Development
5
E.1 Potentially Beneficial Combinations of Herbals with Drugs
E.1.1 Herbs and Those Drugs Which May Potentially Be Complemented
E.2 Herbal Aids for Modifying Substance Abuse
E.2.1 Botanical Adjuncts for Reducing Recreational Drug Use and/or Damage
E.3 Complementing Treatment of Inflammations
E.3.2 Enhancing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
E.3.3 Enhancing Outcomes When Using Analgesics
E.3.4 Protecting Against NSAID-induced Ulcers
E.3.5 Protecting Against Acetaminophen-induced Liver Toxicity
E.4 Enhancing Chemotherapy and Chemoprevention or Reducing the Adverse Effects
E.4.1 Enhancing therapeutic effects of chemotherapy
E.4.2 Reducing adverse effects of chemotherapy
E.4.4 Promoting and/or Enhancing Chemoprevention of Selective Cancers
E.4.5. Reducing Transforming Growth Factor-1 Before, During, &/or After Chemotherapy
E.5 Herbals for Preventing and Healing Radiation Adverse Effects and/or Enhancing
Radiotherapy or Photodynamic Therapy
E.5.4. Protection from Adverse Effects by Cobalt 60 or Cesium 137 Gamma Radiation
E.5.5 Enhancing Antineoplastic Effects of Radiation
E.5.7. Reducing Transforming Growth Factor-1 Before, During, &/or After Radiotherapy
E.6 Herbals and Anti-infection Agents
E.6.1 Botanicals active against antibiotic-resistant strains of bacteria
E.6.2 Botanicals improving antimicrobial efficacy against resistant strains
E.6.3 Botanicals enhancing the ordinary efficacy of antibiotics & antiseptics
E.6.6 Botanicals inhibiting efflux of antimicrobial agents by bacteria
E.6.7 Botanicals enhancing [or reducing] the efficacy of antifungal agents ^
E.6.9 Botanicals enhancing the efficacy of immunizations against infections
REFERENCES
New references citations from 2709 to 3418 can be found at the end of these Updates and Additions.
Reference citations prior to # 2709 are available free on this website in pdf file format for downloading or
printing for personal use.
6
Contraindications, Drug Interactions and/or Complementary Adjuncts
ALOE p. 34
Aloe vera = Aloe barbadensis fresh leaf gel (not the dried sap)
Drug Interactions
Ia. 1) Increased the hypoglycemic effect of glyburide [glibenclamide] when given twice daily for
42 days (PO in human clinical study).122
The juice processed with catalase and removal of anthroquinones and monosaccharides
reduced blood glucose levels to normal in type 2 diabetes with diet-induced obesity, apparently
by decreasing insulin resistance (PO in mice). Plasma insulin was lowered, as were plasma and
liver triglycerides.2741
AMERICAN GINSENG p. 37
Panax quinquefolius root
Contraindications
II. 1) Estrogen-independent proliferation of human breast cancer cell with the alcoholic extract (in
vitro)1664 suggests avoiding regular consumption with a history of breast cancer (speculative).
HOWEVER, a standardized proprietary extract with no effect on the cell cycle significantly
inhibited estrogen-receptor positive breast cancer cell proliferation at concentrations of 500
mcg/ml and higher (in vitro),981 as did a water-extract on the same cells (in vitro).3063 A freeze-
dried water extract of the root significantly reduced proliferation of these estrogen-sensitive
human breast cancer cells, as well as antiproliferation and resistance to stimulated COX-2
expression in estrogen-receptor negative breast cancer cells (in vitro).3062 Though a fresh-root
extract had no effect, a 70% ethanol steam-processed root extract with increased ginsenoside
Rg3, as well as isolated Rb3, significantly decreased proliferative activity of estrogen-receptor
positive and negative human breast cancer cells by arresting the cell cycle in G1-phase (in
vitro).3061 In conjunction with the synergistic effect with chemotherapeutic agents against breast
cancer cells [See Complementary Adjuncts IIb. 1.], the weight of in-vitro evidence now seems to
suggest a potential benefit in breast cancer (speculative).
Drug Interactions
Ia. 1) 3 grams root or more reduced blood sugar in type 2 diabetics treated with sulfonylureas or a
combination with metformin (PO in human study).1114
HOWEVER, in a randomized, placebo-controlled, double-blind, safety study of patients with
74 well-controlled type 2 diabetes mellitus using diet and/or antihyperglycemic medications, 3
g/day of American ginseng ethanolic extract with 10% ginsenosides was used at mealtime as an
adjunct for 12 weeks (orally in human clinical study). Of the 65 on medications, 26 used 1
hypoglycemic drug and 39 used ≥2; of these, 49 used metformin, 43 took sulfonylureas, 11 used
dipeptidyl peptidase-4 inhibitors, and 4 others took acarbose. No changes in kidney, liver or
hemostatic functions were detected, and the severity and number of adverse events did not differ
between the extract and placebo groups.3412
Either 1, 2, 3, 6, or 9 grams of the ground root improved glucose tolerance when given 40
minutes prior to a 25-gram glucose challenge in 10 nondiabetics (PO in human studies).1685,2917
2) After 3 days of warfarin, 2 grams root daily for 3 weeks reduced blood levels and
anticoagulant effect of warfarin (PO in human study).1600
HOWEVER, based on clinical relevance, the pharmacokinetic interaction risk has been
assessed as low (speculative).3222
III. 1) The saponin fraction enhanced phenylephrine vasoconstrictor effect (in vitro).1550
HOWEVER, when 16 hypertensive patients were randomly given 3 grams of root from 6
different farms in Ontario, Canada, for 1 day each, none produced an overall mean change in
blood pressure compared to baseline over a period of 160 minutes (PO in human study). Thirteen
7
were taking 1 or more antihypertensive drugs, including 6 on diuretics, 6 on ACE inhibitors, 3 on
calcium channel blockers, 2 on beta blockers, and 2 on angiotensin receptor blockers. After
monitoring every 10 minutes, increases in mean systolic blood pressure after 140 minutes and
diastolic blood pressure after 160 minutes were countered by a lowered mean diastolic pressure at
100 minutes, compared to mean pressures from 2 days on placebo.2915
2) Using 3 digoxin immunoassays, a American ginseng extract increased the digoxin
measurement results for the fluorescence polarization immunoassay (in vitro).1995
A new analyzer technology from Abbott Laboratories led to deveopment of 2 analyzers, iDig
and cDig, using specific monoclonal antibody against digoxin for which American ginseng does
not interfere with detection of digoxin (in vitro).3435
Ia. + 1) In a randomized blinded study with 175 cancer-related fatigue patients of whom 57% were
still receiving chemotherapy and 18% radiation [previously, 65% received chemo and 38%
radiation], trends toward improvement in fatigue and vitality were seen in the 94 taking 1000 or
2000 mg of root compared to baseline, whereas 81 patients on 750 mg root or placebo showed no
improvements (PO in human clinical study). A total of 40% of patients receiving 1 or 2 gm
ginseng compared to 17% on placebo observed a benefit and were satisfied with the treatment.
No significant differences in toxicities occurred between any of the groups.2916 A follow-up
randomized, double-blind study with 2 gm root with 3% ginsensosides showed a significant
improvement in 138 cancer-related fatigue after 8 weeks with ginseng, compared to 133 on
placebo (PO in human clinical study). The reduction in fatigue was significant after 4 weeks of
the root for only those currently undergoing chemotherapy, compared to placebo in those
receiving treatment.3293
+ 2) A 200 mg daily dose of a proprietary extract, CVT-E002 that consists of 80% polysaccharides
and oligosaccharides and 10% protein, given in separate studies after influenza vaccine in 90%
for 2 or 3 months to 97 elderly subjects in institutions or for 1 month before the vaccination and 3
months afterwards to all 22 elderly adults dwelling in the community, led to a significant
reduction in the incidence of influenza in the institutional groups receiving the extract and
significantly reduced duration of acute respiratory symptoms in the community group,
compared to the 101 and 21 subjects receiving placebo, respectively (PO in human clinical
study).2918,2919
IIa. + 1) Pre-treatment or co-treatment for 3 or 7 days with 50 or 100 mg/kg of the root and
mitomycin C significantly reduced frequency of mitomycin C-induced genotoxicity in bone
marrow and peripheral blood (PO in mice).2922
+ 2) Ginsenoside Rg3, the main ginsenoside in steamed American ginseng roots,2923 when given
with cyclophosphamide for 10 days to animals with tranplanted SKOV-3 ovarian cancer cells,
enhanced the quality and duration of life, reduced averge tumor weight and significantly reduced
angiogenesis more than cyclophosphamide used alone (IP in mice).2924 In other studies, the DNA
damage to bone marrow cells and peripheral lymphocytes caused by cyclophosphamide was
significantly reduced when 20 mg/kg of ginsenoside Rg3 from heat-processed root was given
once daily for 2 days prior (PO in mice)2925 and when exposed to the major fresh root ginsenoside
Rb1 (in vitro).3064 Also, cyclophosphamide-induced bone marrow apoptosis, reduction of
superoxide dismutase and glutathione peroxidase, and increased production of the lipid
peroxidation marker malondialdehyde were all significantly antagonized by Rg3 (PO in mice)2925
and Rb1 (in vitro).3064 In addition, ginsenoside Rh2 from heat-processed root at 10 and 20 mg/kg
significantly enhanced the antitumor effect of cyclophosphamide against B16 melanoma cells
and Lewis lung carcinoma cells, while also significantly reducing cyclophosphamide-induced
genotoxicity and DNA damage to bone marrow red blood cells and peripheral white blood cells,
respectively (PO in mice).2926
+ 3) Pretreatment with 100 and 200 mg/kg of ginsenosides Rb1 or Rg1 caused significant inhibition
of hyperactivity induced by methamphetamine of cocaine (IP in mice). Also,
8
methamphetamine- or cocaine-induced conditioned place preference was significantly inhibited
in those pretreated with 100 mg/kg of ginsenosides Rb1 or Rg1, along with inhibition of the
accompanying dopamine supersensitivity.2929,2931
IIb. 1) A standardized extract (CNT2000) increased the suppression of growth of estrogen-dependent
MCF-7 breast cancer cells synergisticly when combined with tamoxifen, cytoxan,
doxorubicin, paclitaxel (Taxol®) and methotrexate (in vitro).981
HOWEVER, a methanolic extract was shown to bind to alpha- and beta-estrogen receptors
and increase expression of an estrogen-responsive gene, while the water extract was without
effect (in vitro). A methanolic extract of the roots increased MCF-7 proliferation at 5-100 mcg/ml
under low estrogen conditions after 6 days, but a water extract had no effect (in vitro). At higher
concentrations, both extracts inhibited MCF-7 proliferation (in vitro).3294
+ 2) A 70% ethanolic extract of 4-hour steamed roots, with greatly altered ginsenoside content
including 78 mg/g Rg3, 25 mg/g 20R-Rg2, 23 mg/g Rg2, 16 mg/g Rb1, and 12 mg/g Rh2,
increased apoptosis of HCT116 and SW480 colorectal cancer cells maximally when combined
antioxidants N-acetyl cysteine or vitamin C that lowered the reactive oxygen species generated
and increased apoptosis (in vitro).2923
+ 3) In a randomized, placebo-controlled, double-blind 12-week trial with 64 hypertensive
diabetic patients using medications, American ginseng ethanolic extract with 10% total
ginsenosides was taken by 30 patients as an adjunct in dose of 1 gram 3 times daily prior to meals
(PO in human clinical study). In addition to standard diabetic medications, the antihypertensive
drug taken included ACE inhibitors by 15, beta-blockers by 8, calcium channel blockers by 7,
and various fixed combinations by 16, plus several other used by 1 or 2 patients. The addition of
the extract to the medications led to significant decreases in radial arterial stiffness and systolic
blood pressure.3420
AMERICAN GINSENG
^ berry
IIb. 1) A berry extract with 24.5% ginsenoside Rb3 [just over half of total ginsenosides] at 1.0
mg/ml synergistically reduced proliferation of SW-480, HCT-116, and HT-29 human colorectal
cancer cells by G2/M phase arrest, when combined with 5-fluorouracil that arrested cells at the
cell cycle S phase (in vitro).2927
AMLA NEW
Emblica officinalis = Phyllanthus emblica fruit
^ (Indian gooseberry; It. & Port.: Mirabolano emblico; Beng.: amlaki; Punj.: olay; Arab.: haliilaj;
Ch.: an mole; Mal.: nellikka; Nep.: amba; Lao & Thai: ma kham pom)
IIa. 1) At 250 and 500 mg/kg, the aqueous extract given for 7 days before a single 40 mg/kg dose of
cyclophosphamide was shown to inhibit the bone marrow chromosomal mutations induced by
the anticancer drug (PO in mice).2853 At 100 mg/kg the aqueous extract taken for 10 days reduced
immunosuppression of humoral immunity by cyclophosphamide (PO in mice).2855 This may be
due to the reduction of CYP450 levels in the liver, since cyclophosphamide is bioactivated by
CYP450, or it may be due to the increased liver and kidney levels of glutathione, glutathione-S-
transferase, or other detoxification and antioxidant enzymes as shown in animals with both the
aqueous and ethanolic extracts (PO in mice).2853,2854,2855
2) When a 50% ethanolic extract was given at 75 mg/kg 4 hours before exposure to 5 g/kg
alcohol (ethanol) was given to induce hepatotoxicity, it significantly reduced serum
transaminases ALT and AST and interleukin(IL)-1beta similar to 5 mg/kg silymarin, as compared
to controls (PO in rats). Similarly, when 75 mg/kg of the amla extract was given daily for 7 days
after 21 days of 4 g/kg/day of ethanol, ALT and IL-1beta were reduced greater than no treatment
and slightly better than 5 mg/kg silymarin.2856 Amla aqueous extract at 250 mg/kg/day following
9
chronic alcohol liver damage lowered lipid peroxidation and elevated liver antioxidant enzymes
(PO in rats).3152 In rat liver cells exposed to alcohol, the ALT was also shown to be significantly
reduced by the extract at 0.5 mg/ml (in vitro).2856
The component ellagic acid at 60 mg/kg has been shown to reduce effects of hepatotoxicity
induced by 7.9 g/kg ethanol daily for 45 days (PO in rats).3153-3155 This includes a reduction of the
liver fibrotic markers,3153 improved body weight and circulatory antioxidant status,3154 decreased
lipid levels,3154,3155 and reduced plasma AST, ALT, and peroxidative markers.3155
3) A 4:1 strength dry aqueous extract of the dried fruit given at 300 mg/kg for 90 days with the
antituberculosis treatment with isoniazid, rifampicin, and pyrazinamide significantly prevented
necrotic changes to the liver due to the drugs' hepatotoxicity (PO in rats). The effect was
enhanced when 100 mg/kg of the aqueous extract of the stem of gulancha (Tinospora cordifolia)
was added, and even at half this dose was comparable to silymarin at 50 mg/kg in reducing liver
damage, though gulancha extract was not effective on its own.2857 A 50% hydroalcoholic extract
of amla fresh fruit was shown to significantly reduce the increases in transaminases ALT and
AST, alkaline phosphatase, and bilirubin induced by the combination of isoniazid, rifampicin, an
pyrazinamide, similar to N-acetyl cysteine, while reducing lipid peroxidation and increased
glutathione content in liver cells (PO in rats).2858
IIb. 1) Ethanolic extract of the fruit was shown to protect against cardiotoxicity of doxorubicin by
increasing the IC50 12-fold without impacting its antitumor activity on HeLa cells (in vitro).2859
The aqueous extracts of the dried fruit increased the cytotoxicity of both doxorubicin and
cisplatin against human liver cancer cells and lung cancer cells (in vitro).2860
ANISE
Pimpinella anisum seed/fruit
Drug Interactions
IIa. 1) Anise essential oil containing 88.5% anethole was given at the human equivalent dose of 0.3
mg/kg for 5 days prior to a single dose of drugs that are either sedatives or antidepressants (PO
in mice). Combined with codeine, the anise oil significantly increased the analgesic activity. The
combination with midazolam led to greater motor impairment, while the oil also increased the
effect of diazepam by further decreasing motor activity. So, the sedative effects of these 3 drugs
were all enhanced, though anise oil alone was not sedative. On the other hand, anise oil
significantly reduced the sleeping time induce by pentobarbital. The antidepressant effect of
fluoxetine and imipramine were also diminished by anise oil pretreatment. The potential
interactions of anise essential oil with drugs impacting the central nervous system suggests that
these combinations in humans should be avoided (speculative).3535
ARJUNA
Terminalia arjuna bark
Ia. 1) An extract made by combining a 90% ethanolic extraction followed by a water extraction and
given at 500 mg 3 times/day for 2 weeks improved symptoms of Class IV refractory chronic
congestive heart failure compared to placebo, when given in a crossover design to 12 patients
taking digoxin, along with the diuretic drugs furosemide and spironolactone (PO in human
clinical study). All were also administered potassium supplements. In addition, vasodilator use
included 8 on enalapril, 3 on captopril, 1 on nifedipine, and 3 on isosorbide dinitrate. In a
continuation of the trial signs and symptoms continued improving for 2-3 months and were
maintained, while diuretic dosages were reduced.2661
2) When 58 patients with chronic stable angina functional NYHA class II or III were given 500
mg of the ethanolic/aqueous combined extract 3 times daily for 1 week in a randomized, double-
blind, crossover trial, the incidence of angina and use of the anti-angina drug isosorbide dinitrate
10
was significantly less than when taking placebo for 1 week (PO in human clinical study). Patients
had stopped their regular use of isosorbide mononitrate and beta-blockers during the study.3286
ARNICA p. 41
*Arnica montana flowers
Ia. + 1) A preparation made with 50 g fresh herbal 1:20 tincture in 100 g of gel was compared to a 5%
ibuprofen gel for 21 days on hand osteoarthritis in 204 randomized subjects for whom 500 mg
acetaminophen (paracetemol) was allowed not more than once daily for the first 20 days as an
"escape treatment" (TP in human clinical study). Gels were applied locally 3 times daily and left
on for an hour; this was well tolerated, though skin symptoms resulted for 6 in each group. The
gels were equivalent in improving pain and hand function, as well as in reducing joint stiffness
and its duration; the arnica and ibuprofen groups' average use of a acetaminophen was 11.2 and
11.3 tablets, respectively, over 3 weeks. Efficacy was assessed as good/very good by physicians
and patients in 57% and 59% of cases, respectively, for ibuprofen versus in 64% of cases by both
physicians and patients for arnica.2805
2) A combination spray of arnica tincture with hydroxyethyl salicylate for 228 patients with
acute unilateral ankle sprain produced significantly improved pain on motion after 3-4 days,
compared to 228 patients who used a spray with only hydroxyethyl salicylate, 57 patients who
only used arnica tincture spray, or 57 patients who used a placebo spray (TP in human clinical
study). A dose of 0.5 ml was applied locally 4-5 times daily for 10 days, and the combination also
showed better pain relief after 10 days. There were no significant differences in tolerability
between the groups. All 4 sprays had a 78% ethanol content along with camphor and essential
oils to provide a uniform fragrance.3090
ASHWAGANDHA p. 42
Withania somnifera root
Ia. + 1) In new patients with pulmonary tuberculosis receiving standard drug treatment with the
combination of rifampicin, pyrazinamide, isoniazid, and ethambutol, those 17 randomized to
also receive 1 gm twice daily of ashwagandha had no evidence of acid-fast bacteria in the sputum
after 28 days, whereas 6 of the 17 on drugs alone had positive sputum tests for the TB bacteria
(PO in human clinical study). In a further study of 40 other new pulmonary TB patients, the 20
receiving the drugs with ashwandha had a greater and more rapid lowering of symptom scores on
days 15 and 29, along with higher total white blood cell counts, hemoglobin, body weight, and
IgM antibodies and lower erythrocyte sedimentation rate. The ashwagandha group had a zero
bacterial load count by day 26, while the drugs alone regimen group was still positive after 29
days. The blood levels of pyrazinamide and isoniazid were also higher in the ashwagandha group
after dosing on day 29 than in the drugs alone group, while liver function tests significantly
improved for those using ashwaganda but the drug group the opposite trend.3233
+ 2) The 44 patients with breast cancer who received 6 grams daily of an ashwagandha root
extract, 50% of whom received a taxotere, adriamycin, cyclophosphamide combination plus
48% receiving cyclophosphamide, epirubicin, and 5-fluorouracil, had significantly less
treatment-related fatigue and significantly improved quality of life in 7 of 18 symptoms,
compared to the 41 control patients who received only the chemotherapy treatments, 30% with
cyclophosphamide, epirubicin, and 5-fluorouracil and 70% with the taxotere, adriamycin,
cyclophosphamide combination (PO in human clinical trial).3252
+ 3) In a randomized, placebo-controlled, double-blind trial with 30 patients diagnosed with
obsessive-compulsive disorder [OCD] and being treated with Selective Serotonin Re-uptake
Inhibitors [SSRI's], half were given 120 mg daily of an ashwagandha extract for 6 weeks (PO in
human clinical trial). In changes to the baseline values for the Yale-Brown Obsessive-
11
Compulsive Scale [Y-BOCS], the ashwagandha group had a significantly greater reduction of -8
for the Y-BOCS score, compared to -2 for the placebo group. No adverse events were reported
during the trial, so the extracts appears to be both effective and safe as an SSRI adjunct in treating
OCD.3548
IIa. 7) After using root extract, tolerance to morphine analgesia was inhibited, and morphine
dependence was blocked (PO in mice study).1277
In addition, with 14-day treatment during concurrent morphine use 100 mg/kg of a
standardized ashwagandha extract significantly reduced spontaneous morphine withdrawal
syndrome symptom severity after 1 and 3 days and the spine density in the nucleus accumbens
shell, but not when given only during the first 3 days of withdrawal (IP in rats).3466
+ 8) The kidney toxicity induced by the antibiotic gentamicin was significantly reversed by 500
mg/kg ashwagandha root extract given for 14 days before and concurrently for 8 days with
gentamicin (PO in rats). The kidney tubular necrosis and toxicity symptoms were reduced
including increased kidney weight, urea, cratinine, urinary protein and glucose, and significant
reductions in body weight and potassium.3253
ASIAN GINSENG p. 44
Panax ginseng root
Contraindications
II. 2) Do not use with type 1 diabetes (speculative)893 because of ginseng extract’s anti-
hyperglycemic effect (PO in human clinical study).109
In a randomized, placebo-controlled, double-blind trial, 12 undiagnosed patients with
moderately elevated fasting glucose given 960 mg per day of a hydrolyzed ginseng extract for 8
weeks, the fasting and postprandial glucose levels were significantly decreased, compared to 11
in the placebo group (PO in human clinical study).3452
Drug Interactions
Ia. 2) Uncharacterized "ginseng" with CYP 3A4 substrate nifedipine increased the drug peak
plasma concentration 29% (PO in human study).1728
HOWEVER, a 500 mg dose of a standardized extract given twice daily for 28 days to 12
subjects resulted in significant decreases in AUC, half-life and maximum concentration of the
CYP 3A4 substrate midazolam, indicative of induction (PO in human study). There was no effect
on the Pgp substrate fexofenadine.2965
3) A randomized trial using ginseng doses of 2 grams 3 times daily for 12 weeks in 19 patients
with diabetes type 2, in combination with diet alone or diet plus hypoglycemic drugs in 14
resulted in reduction in oral glucose tolerance test indices by 8-11% and plasma insulin by 33-
38% (PO in human clinical study).2042
In a randomized double-blind crossover study with 20 type 2 diabetics using diet and/or oral
hypoglycemic agents to treat their diabetes, 740 mg of ginseng t.i.d. for 4 weeks led to
significantly lower fasting plasma glucose and assessed insulin resistance compared to placebo
(PO in human clinical study). Oral glucose tolerance tests were unaffected, though both the
insulin response and fasting insulin tended to be reduced by ginseng.2788
Ib. + 5) A man taking the known liver toxin imatinib for 7 years without incident developed acute
lobular hepatitis 3 months after he began daily consuming an energy drink containing ginseng
extract (PO in human case report). When the imatinib and energy drink were stopped and
prednisone given for 19 days, the liver enzyme levels were normalized for 4 weeks. [According
to the drink label, the product also contained taurine, caffeine, guarana extract, carnitine fumarate,
vitamins B3, B6, and B12.] When the CYP 3A4 substrate imatinib was reintroduced for 3
months, no liver enzyme elevations occurred.2764 Asian ginseng root has been shown to inhibit
CYP 3A4 and thereby increase the level of the drug substrate (PO in human study).1728
II. 4) While feeding with fructose-rich chow, treatment with 125 mg/kg ginseng root 3 times daily
after 5-15 days reduced the delay in the glucose-lowering response to 10 mg/kg IP tolbutamide
12
(PO in rats). This is explained by tolbutamide increasing endogenous insulin secretion in response
to developing insulin resistance, and ginseng acting to increase insulin sensitivity. Ginseng given
alone for 3 days with fructose-rich chow did not result in elevated plasma glucose, whereas it did
in controls.3520
III. 3) Using 5 digoxin immunoassays on 2 liquid Asian ginseng extracts and 1 capsule, only one of
the liquid extracts increased the digoxin measurement results only for the fluorescence
polarization immunoassay (in vitro, ex vivo with rats).1352,1995
A new analyzer technology from Abbott Laboratories led to deveopment of 2 analyzers, iDig
and cDig, using specific monoclonal antibody against digoxin for which Asian ginseng does not
interfere with detection of digoxin (in vitro).3435
Ia. 3) Following surgery for stage III gastric cancer, red ginseng powder doubled survival rates in
patients given 5-fluorouracil and cisplatin (PO in human clinical study).1382
The aqueous extract of the steamed Korean red ginseng root at a concentration of 2.5 mcg/ml
containing ginsenosides Rb1 and Rg1 significantly attentuated auditory hair cell damage caused
by cisplatin (in vitro). This prevention of ototoxicity was due to inhibition of the free radical
generation and apoptosis by cisplatin (in vitro).2725
+ 5) Just under half of the 61 patients between the ages of 50-80 years with Alzheimer's disease
who were being treated with donepezil, galantamine, memantine, or rivastigmine were also
given 4.5 g/day or 9.0 g/day of Korean red ginseng root powder for 12 weeks and monitored by
cognitive tests (PO in human clinical trial). At the open-label study's end, those receiving the
higher ginseng dose had significantly lower scores on the Alzheimer's Disease Assessment Scale
[ADAS] and its cognitive component and the Clinical Dementia Rating scale.3059 In a similar 12-
week study by the same researchers with Alzheimer's patients ages 47-83 years, 39 active
treatment controls and 49 additionally receiving 4.5 g/day Korean white ginseng root powder and
9 given 9 g/day ginseng, significant improvements were shown on the ADAS cognitive subscale
and the mini-mental state examination for the ginseng groups (PO in human clinical study). There
were no significant differences in scores between the 2 ginseng doses. When the ginseng use was
stopped, the improved scores decreased over 12 weeks to control levels.3060
IIa. + 3) Pretreatment with 100 and 200 mg/kg of ginsenosides Rb1 or Rg1 caused significant inhibition
of hyperactivity induced by methamphetamine or cocaine (IP in mice). Also,
methamphetamine- or cocaine-induced conditioned place preference was significantly inhibited
in those pretreated with 100 mg/kg of ginsenosides Rb1 or Rg1, along with inhibition of the
accompanying dopamine supersensitivity.2929,2931 The inhibition of methamphetamine-induced
hyperlocomotion and conditioned place preference by 50 and 150 mg/kg of unspecified
ginsenosides was associated with stimulation of adenosine A2A receptors (IP in mice).2930
+ 4) After 4 weeks of cyclosporine use, blood glucose increased and insulin decreased due to
oxidative pancreatic injury to beta cells, but 0.4 g/kg daily of red ginseng extract given
concurrently ameliorated the high blood glucose and glucose intolerance (PO in mice). The
ginseng extract also reduced pro-inflammatory molecules and apoptotic cell death.3522
ASTRAGALUS p. 51
Astragalus membranaceus, Astragalus mongholicus root
IIa. + 3) Equal quantities of astragalus root and dong quai (Angelica sinensis) root were extracted with
ethanol and water, the extracts combined, and 2.1 grams daily given with or without the ACE
inhibitor enalapril to monitor kidney fibrosis and compared to enalapril alone (PO in rats). The
tubulointerstitial fibrosis was reduced by the herbal extract and enalapril separately along with
transforming growth factor-1 [TGF-1], but the herbal-drug combination had the greatest effect
by significantly reducing TNF-, collagen accumulation, fibroblast activation, tubular cell
apoptosis more than enalapril alone.2728 A decoction of equal parts of the 2 roots given at the
13
same dose was previously shown a decrease in TGF-1 puromucin-induced nephrosis similar to
enalapril (PO in rats),2729 while 3.6 g/kg daily dose of a 5:1 mixture of astraglus and dong quai
roots, respectively, as a decocted extract also modestly decreased kidney TGF-1 mRNA
expression following streptozotocin-induced damage, similar to the ACE inhibitor benazepril (PO
in rats).2730
BARBERRY p. 53
*Berberis vulgaris root bark
Contraindications
II. 1) Do not use in jaundice in newborns, from hemolytic anemia, or unconjugated
hyperbilirubinemia as Gilbert’s syndrome and Crigler-Najjar syndrome (speculative).777,1890
HOWEVER, when berberine-containing herbs were given in herbal concoctions according to
traditional dosage and indication to 20 patients with chronic cytopenic hematological conditions,
though 3 patients with thalassemia intermedia had transient elevation of serum bilirubin, there
was no associated aggravation of anemia or liver dysfunction (PO in human clinical study).3108
Drug Interactions
Ia. 1) [The book entry for berbamine and chemotherapy has now appropriately been moved to
Complementary Adjuncts #Ia. 3).]
+ 1) Berberine at 300 mg 3 times daily for 14 days in 17 healthy males significantly increased the
bioavailablity of CYP 3A4 substrate midazolam by 40% and its maximum plasma concentration
by 38%, and significantly decreased its oral clearance by 27% (PO in human study).3238
3) The combination of 1500 mg berberine daily for 3 months in 43 type 2 diabetes patients with
one or more oral hypoglycemic medications including sulfonylureas, metformin acarbose,
and/or insulin resulted in lower blood sugar through week 12 (PO in human clinical study).2315
In 58 type 2 diabetic patients, 1 gm daily of berberine significantly lowered fasting and
postload plasma glucose and HbA1c compared to 52 diabetics on placebo, along with
significantly reducing the triglycerides, total cholesterol, and LDL-cholesterol, body weight, and
systolic blood pressure (PO in human clinical study).2907 In 50 type 2 diabetic patients randomly
selected to use 1 gm berberine daily, the 26% and 18% significant reductions in fasting blood
glucose and HbA1c were equivalent to those of the 26 and 21 diabetic patients who used
metformin or rosiglitazone, respectively (PO in human clinical trial). Only the berberine group
had a significant reduction of triglycerides. Also, in another group of 18 hepatitis C and 17
chronic hepatitis B patients with type 2 diabetes or impaired fasting glucose, 1 gm/day berberine
significantly reduced fasting blood glucose, triglycerides, and the transminases ALT and AST
(PO in human clinical trial).2908
8-hour urinary ratio of the CYP 2D6 substrate dextromethorphan to its metabolite dextrorphan
by 9-fold (PO in human study).3238
+ 5) Berberine at 900 mg daily in 17 healthy males for 14 days doubled significantly the 8-hour
urinary ratio of the CYP 2C9 substrate losartan to its metabolite E-3174 (PO in human
study).3238
II. + 2) In doses of 30 mg/kg berberine for 2 weeks, the Pgp substrates digoxin and cyclosporine had
significantly increased maximum serum concentration and bioavailability compared to controls,
indicating berberine inhibition of Pgp drug efflux (PO in rats).3105 Likewise, the oral
bioavailability of ketoconazole was significantly increased by berberine given at 60 mg/kg (PO
in rats). Since ketoconazole is both a substrate and an inhibitor of Pgp and berberine is a Pgp
substrate, the pharmacokinetic effect of each on the other may lead to pharmacodynamic
synergism against fungal infections (speculative).3104
III. 3) [See Complementary Adjuncts Ia. 4) below.]
14
Ia. 3) [Moved from Drug Interactions Ia. 1).] The alkaloid berbamine given at 150 mg daily for 1-4
weeks helped reverse leukopenia induced by cancer chemotherapy or radiotherapy, especially
when the white blood cell count was not less than 1000/mm3 from anticancer drugs (PO in human
clinical study).398
+ 4) When 500 mg berberine hydrochloride was given twice daily with simvastatin 20 mg once
daily for 2 months to 23 patients in a randomized trial for high cholesterol, the 31.8% reduction
in LDL cholersterol was significantly better than the 23.8% with berberine in 24 patients or the
14.3% with simvastatin in 16 patients used alone (PO in human clinical study). For triglycerides,
the combinations reduced these by 38.9%, significantly better than 22.1% for berberine or 11.4%
for simvastatin alone. Similar results were obtained for total cholesterol. No adverse effects were
observed in any group. These results reflected those obtained in animals given 90 mg/kg/day
berberine and/or 6 mg/kg/day simvastatin (PO in rats).2905 In 58 type 2 diabetic patients, 1 gm
daily of berberine significantly lowered triglycerides, total cholesterol, and LDL-cholesterol
compared to 52 diabetics on placebo, along with significantly reducing the fasting and postload
plasma glucose, HbA1c, body weight and systolic blood pressure (PO in human clinical
study).2907
In human liver-derived cells, berberine was found to have an additive effect with lovastatin (in
vitro). Since lovastatin did not reduce the effect of berberine, this indicated a different mechanism
of action for the two (in vitro).1656
IIa. + 4) Berberine at 200 mg/kg given for 10 days with cocaine significantly inhibited the excessive
locomotor activity induced by an acute dose of cocaine 4 days later (PO in rats). The effect was
associated with a significant decrease in tyrosine hydroxylase activity in the ventral tegmental
area with the berberine, indicating a reduction in the production of dopamine (PO in rats). This
suggests that berberine may help reduce the chronic cocaine psychological dependence
(speculative).2753
+ 5) When taken with a high cholesterol and high fat diet, berberine at 100 mg/kg daily combined
with 1% plant stanols in the diet for 6 weeks significantly and synergistically reduced plasma
total cholesterol, non-HDL cholesterol, and triglycerides compared to controls (PO in rats).2932
When the same doses of berberine and plant stanols were used in a normal diet for 4 weeks, the
combination significantly reduced plasma total cholesterol, non-HDL cholesterol, and
triglycerides compared to controls and significantly more than the plant stanols alone (PO in
hamsters). Berberine and stanols synergistically inhibited fractional cholesterol absorption and
increased gene expression of CYP7A1 and CYP27A1 that convert cholesterol to bile acids.2933
The berberine and stanols alone or in combination showed no biochemical toxicity on the liver
(PO in rats);2932 berberine and the combination even significantly reduced plasma ALT
concentrations (PO in hamsters).2933
+ 6) The combination of 1 mg/kg berberine with 0.5 mg/kg amphotericin B increased the survival
for disseminated candidiasis to 36 days from 12 days for controls and 17 days and 14 days,
respectively, when these 2 antifungal agents were used separately (IP in mice).3107
+ 7) Compared to those injected with 2.5 mg/kg doxorubicin alone every other day for 14 days,
those injected with 60 mg/kg berberine an hour prior to the drug had less cardiotoxicity as shown
by significantly smaller increases in mortality, LDH activity, myocardial injury, and QRS
duration (IP in mice). This indicates a potential protective role of berberine against heart damage
by doxorubicin.3148
BILBERRY p. 58
Vaccinium myrtillus fruit
Ia. + 1) When 80 mg bilberry (Vaccinium myrtillus) extract with 36% anthocyanins and 40 mg
Pycnogenol with 70% procyanidins as a standardized combination was given once daily in the
morning to 79 ocular hypertension patients either alone or together with latanoprost eye drops
15
and compared to latanoprost alone, the extract combination with the drug was best for lowering
intraocular pressure and enhancing retinal blood flow (PO in human clinical study). The extract
alone eventually was similarly effective as the drug for lowering intraocular pressure, but it took
24 weeks for the extract compared to only 4 weeks with latanoprost. The only adverse effects
were those related to latanoprost.2966
IIa. + 2) Supplemening the diet with 1% bilberry extract led to significantly reduced myocardial
damage, cardiac glutathione depletion, and serum lipid peroxidation following a 15 mg/kg dose
of IP doxorubicin (PO in rats).3514 While being given 100 mg/kg of a bilberry methanolic extract
for 10 days, 15 mg/kg doxorubicin was administered IP on day 7 (PO in rats). In comparison to
controls, after day 10 this extract had likewise reduced cardiac glutathione depletion and
malondialdehyde formation. The reduction of cardiac antioxidant enzyme activities for catalse,
superoxide dismutase, and gluthione peroxidase was significantly ameliorated by the extract. It
also decreased serum levels of troponin I and activities of lactate dehydrogenase, creastine
phosphokinase, creatine kinase-MB. Finally, the ECG and pathological changes found in controls
were alleviated by the extract.3515
When 500 mg/kg of bilberry extract was given daily for 10 days in rats treated with 10 mg/kg
doxorubicin, it partially prevented the hematopoietic damage resulting in reductions in red blood
cell count, bone marrow cell counts, and hemoglobin level (PO in rats).3514
BITTER MELON p. 59
Momordica charantia fruit / juice and seeds
Contraindications
I. 1) Avoid in pregnancy due to the emmenogogue and abortifacient effects (empirical).74
The glycoproteins, a- and b-momorcharin in the seeds have shown abortifacient activity in early
pregnancy (IP in mice)3056 by inhibiting the differentiating endometrium (in vitro, IP in mice),3057
and also teratogenic changes during organogenesis due to effects on the visceral yolk sac (in
vitro).3058
II. 1) It should not be employed for insulin-dependent (type 1) diabetes (speculative),893 due to
potentially disruptive hypoglycemic effects, as shown in type 2 diabetic humans using the freeze-
dried juice (PO in human study).3476
BITTER ORANGE p. 60
Citrus aurantium fruit, juice, or peel
Drug Interactions
I.a. 1) The juice consumed by 9 subjects at a dose of 200 ml significantly increased
dextromethorphan bioavailability during first-pass metabolism both by inhibiting intestinal
CYP 3A metabolism and affecting an intestinal transport protein, rather than by inhibition of
CYP 2D6 (PO in human study).2666
HOWEVER, a product standardized to 4% synephrine and given to 12 subjects at a dose of
700 mg daily did not affect metabolism of midazolam or debrisoquin by CYPs 2D6 or 3A4,
respectively, but it was devoid of the CYP3A4 inhibitor 6',7'-dihydrooxybergamottin (PO in
human study).1589
2) Bitter orange juice in a single 240 ml dose also increased felodipine bioavailability (PO in
human study), due to 6',7'-dihydroxybergamottin, bergamottin, and begapten inhibiting intestinal
CYP3A4.1729 In addition, the juice reduced enterocyte CYP3A4 concentrations (PO in
humans).1031
HOWEVER, the bioavailability of indinavir was not impacted by consumption with 240 ml of
bitter orange juice in 13 healthy subjects, though there was a delay in indinavir absorption (PO in
human study).2588 Also, one dose of 240 ml of the juice did not influence cyclosporine
metabolism in 7 healthy subjects (PO in humans), probably because of a lack of effect on Pgp by
6',7'-dihydroxybergamottin (in vitro).1031
16
III. 2) Use of the juice with substrates of CYP3A4 may increase the absorption (speculative), due a
40% reduction of this isozyme (PO in humans).1031
The decoction of the fruit and unripe fruit were slightly inhibitory of testosterone metabolism by
CYP3A4 (in vitro).1633
BLACK COHOSH p. 61
*Actaea racemosa = Cimicifuga racemosa roots/rhizome
Contraindications
I. 3) Signs or symptoms of liver dysfunction suggest discontinuation due to its association with
hepatotoxicity in cases in Europe (empirical).1901
HOWEVER, when 87 healthy postmenopausal women with no evidence of liver disease
received a daily dose for 12 months of 40 mg dry extract from black cohosh made with 58%
ethanol, they were assessed for hepatic function. No significant changes were found in total
hepatic blood flow or any liver function tests (PO in human clinical study).2994
Ia. 2) Solid black cohosh extract was given randomly for 1 year with tamoxifen to 90
premenopausal breast cancer survivors and compared to 46 using tamoxifen alone (PO in
human clinical study). About 74% of those on only tamoxifen had severe hot flashes,
significantly more than the 24% who combined it with extract.1655
Using a 40% isopropenolic extract tablet derived from 20 mg of root following primary cancer
treatment, 47 breast cancer patients on tamoxifen with menopausal symptoms that were severe on
average used 2 tablets daily for 4 weeks, then 24 adjusted the daily black cohosh tablet dose to 4
[n=15], 3 [n=3], or 1 [n=2] or changed to a product combining the extract with St. John's wort
(Hypericum perforatum) extract [n=4] (PO in human clinical study). Significant improvements in
total symptoms scores and subscores for vegetative symptoms and psychic symptoms occurred at
1, 3, and 6 months, with no adverse effects attributed to the extract. The most severe symptoms of
hot flashes, sweating, and sleep problems improved the most. Of the 35 who completed the 6-
month, open, uncontrolled trial, 30 wanted to continue its use.2814
BLACK CUMIN p.66

Nigella sativa seed
Ia. 1) Chemical war victims from mustard gas inhalation on salbutamol and corticosteroids
required less of these after taking black cumin extract (PO in human clinical study).2489
In a 3-month randomized study with 29 asthma patients taking inhaled corticosteroids, mostly
using beclomethasone or fluticasone inhalers, and oral corticosteroids, theophylline, and beta-
agonists, wheezing and coughing and asthma severity were significantly improved by the end of
the study with 15 using black cumin decoction compared to 14 controls, along with decreased use
of all of the drugs by the extract group and no drug reduction by control subjects (PO in human
clinical study).2988 In a group of 15 moderate to severe asthma patients on medications who
temporarily and briefly suspended use of theophylline and beclomethasone or fluticasone inhalers
but continued with prednisolone use, bronchodilation from boiled black cumin extract at 50 or
100 mg/kg was significantly improved compared to the corticosteroid alone, though significantly
less when compared to prednisolone with theophylline or salbutamol (PO in human clinical
study).2989
+ 2) Doses 3 times daily of 250 mg or 500 mg of the powdered seed significantly and dose-
dependently reduced acute opiate withrawal symptoms compared to placebo in an open study of
50 opioid addicts treated for 12 weeks and as in-patients for the first 12 days (PO in human
clinical study). Based on historical controls, craving and relapses were also reduced. Diazepam
was used to some to help sleep.2982
17
+ 3) In 40 females with rheumatoid arthritis taking the antirheumatic drugs methotrexate,
hydroxychloroquine, diclofenac, and folic acid, 500 mg of seed oil given twice daily for a
month significantly decreased disease scores, along with fewer swollen joints and shorter
morning stiffness duration, compared with results after 1 month of placebo (PO in human clinical
study).3114
+ 4) In 21 patients with non-ulcer Helicobacter pylori dyspepsia who were receiving omeprazole,
2 grams of seed powder daily for 4 weeks was effectively in eradicating the H. pylori in 66.7%
(PO in human clinical study). The difference between this outcome and the 82.6% eradication
from use of triple therapy with clarithromycin, amoxicillin, and omeprazole was not statistically
significant.3312
IIa. 2) The use of thymoquinone at 5 mg/kg daily with ifosfamide reduced the severity of the drug-
induced Fanconi syndrome with its kidney damage (PO in rats), while the same combination
used in treating Ehrlich ascites carcinoma xenograft significantly enhanced antitumor effects,
along with lower mortality rate and less weight loss, compared to use of ifosfamide alone (PO in
mice).2431
+ 3) The hepatotoxicity caused by acetaminophen as shown by significant increases in ALT, total
nitrate/nitrite, and lipid peroxide and decreased glutathione was prevented by 5 days of 2
mg/kg/day of thymoquinone (PO in mice). The effect was apparently not due to influence on
metabolic activation of acetaminophen.2983
+ 4) When the seed oil was given at 880 mg/kg for 2 weeks before a 1 ml dose of ethanol, it
significantly reduced formation of stomach ulcers by increasing mucosal glutathione levels and
mucin and decreasing mucosal histamine (PO in rats).2984 Thymoquine given at 20 mg/kg reduced
ethanol-induced stomach ulcers and the associated lipid peroxidation and glutathione depletion
(PO in rats).2987
+ 5) The cardiotoxicity induced by doxorubicin as indicated by elevated serum lactate
dehydrogenase and creatine phosphokinase was prevented with 5 days of pretreatment and 2 days
of concurrent treatment with 10 mg/kg daily of thymoquinone (PO in rats). This protection is
likely due to thymoquinone's demonstrated superoxide radical scavenger potency and its
inhibition on lipid peroxidation (in vitro).2985
+ 6) The antitumor effect of gemcitabine and/or oxaliplatin for 2 weeks against orthotopic
pancreatic cancer was significantly increased by 25 days of treatment before, during, and after
with 3 mg thymoquinone, based on tumor weight, while also reducing local invasion and nodal
metastasis (PO in mice). The effect of pretreatment with thymoquinone also reduced pancreatic
cancer cell growth in 3 cell cultures due in part to chemosensitization from down-regulation of
NF-B (in vitro).2986
7) Injections of 80 mg/kg gentamicin for 8 days resulted in kidney toxicity with significant
increases in serum creatinine, BUN, TBARs, and total nitrate/nitrate and decreases in kidney
glutathione, glutathione peroxidanse, catalase, and ATP levels were noted, but giving the drug
together with 50 mg/L thymoquinone in drinking water for 8 days completely reversed all of the
changes and kept the damage markers control levels (PO in rats).3259
BLACK PEPPER p. 67
Piper nigrum fruit
Drug Interactions
Ia. + 4) A single dose of the potent non-nucleoside inhibitor of HIV-1 reverse transcriptase,
nevirapine [a CYP 3A substrate] had 120% greater maximum concentration and 170% increased
bioavailability in 8 healthy subjects when taken after 6 days of piperine compared to placebo in a
crossover trial (PO in human study).3132 Based on clinical relevance, the pharmacokinetic
interaction risk has been assessed as low for use of black pepper as a condiment for flavoring
food but high for Pgp and CYP3A4 substrates with piperine in doses in excess of 10 mg
(speculative).3222
18
Ia. 1) Piperine increased serum concentrations of curcumin and increased curcumin bioavailability
by 2000% (PO in human study).1533
The significant improvements by 200 mg/kg oral curcumin of chronic stress impaired memory
performance and serum cortisone, along with oxidative stress parameters including elevated
malondialdehyde and decreases in reduced glutathione, superoxide dismutase and catalase, were
significantly enhanced with the addition of 20 mg/kg piperine (PO in rats).3396
IIa. + 1) Piperine at 70 mol/kg increased plasma bioavailability of the chemopreventive agent
epigallocatechin gallate [EGCG] in green tea by 1.3-fold when given concurrently compared to
EGCG given alone (PO in mice). Piperine also increased the maximum plasma concentration of
EGCG by inhibiting glucuronidation in mice intestines by 40%. Likewise, the gluruonidation of
EGCG was inhibited in human HT-29 colon adenocarcinoma cells (in vitro). Piperine also
increased EGCG transit time in the intestines (PO in mice).2935
+ 2) Black pepper as 0.5%, or piperine as 0.02%, of the diet for 8 weeks prevented mucosal
stomach damage by ethanol (alcohol) by significantly increasing activity of the endogenous
antioxidant enzymes superoxide dismutase, glutathione reductase, and glutathion-S-transferase in
the stomach and intestinal mucosa and increasing mucin content in stomach mucosa, compared to
having no exposure to the spice (PO in rats).3347
+ 3) Increased bioavailability and maximum concentration of a single dose of the
chemopreventive compound emodin was found when 20 mg/kg was combine with 20 mg/kg of
piperine (PO in rats). Emodin glucuronidation in the intestines and liver that normally reduces
emodin bioavailability was greatly inhibited.3459
+ 4) The mineral absorption of calcium, iron, and zinc were all significantly improved with the
addition of 0.02g% of piperine to the diet, compared to the same diet without piperine (PO in
rats). Calcium absorption was improved the most. Piperine increased the uptake of calcium better
than either capsaicin or ginger.3471
BLACK RASPBERRY NEW

^ Rubus occidentalis fruit and seeds
IIa. 1) The component ellagic acid at 60 mg/kg has been shown to reduce effects of alcohol
hepatotoxicity induced by 7.9 g/kg ethanol daily for 45 days (PO in rats).3153-3155 This includes a
reduction of the liver fibrotic markers,3153 improved body weight and circulatory antioxidant
status,3154 decreased lipid levels,3154,3155 and reduced plasma AST, ALT, and peroxidative
markers.3155
BOLDO p. 73
Peumus boldus leaves
Drug Interactions
Ib. + 2) A 78-year-old man with diabetes, hypertension, and a renal transplant 5 years earlier was
taking 2 mg tacrolimus twice daily consistently, but suddenly tested for having a significantly
low level of <3 ng/ml after taking 600 mg of boldo leaf extract daily (PO in human case report).
He repored no complaints, and physical exam was normal. On stopping the boldo, within a week
the tacrolimus level rose to 6.1 ng/ml using the same dose. The prior subtherapeutic dose may
have been due to an interaction with boldo (speculative).3527
BORAGE
*Borago officinalis
SEED OIL p. 75
19
IIa. + 1) In conjunction with a high-fat diet, when borage oil was given at 150 mg/kg daily for 30 days
along with 4 g/kg ethanol and compared to the effects of inducing steatohepatitis with the
alcohol alone in other subjects, antioxidant protection was observed from the oil (PO in rats). The
addition of the borage oil decreased lipid accumulation in the liver and significantly reduced
serum ALT and GGT activity and total liver CYP450, triglycerides, and peroxidation products
that had all been significantly elevated by the ethanol. The oil, which contained 19.5% gamma-
linolenic acid (GLA) and 4.3% dihomo-GLA, also significantly increased the reduced glutathione
in the liver that had significantly decreased from alcohol alone.3234
BURDOCK p. 79
Arctium lappa root
Ia. + 1) A randomized, placebo-controlled, double-blind study of 36 patients with knee osteoarthritis
used 3 cups [2 g/150 water each] daily of burdock root tea for half, while the control half used 3
cups of boiled water (PO in human clinical study). Both glucosamine daily and acetaminophen
twice daily were considered for each patient. After 42 days, the burdock tea group had
significantly lower levels of the lipid peroxidation marker malondialdehyde, as well as
inflammatory markers interleukin-6 and high sensitivity C-reactive protein.3539
IIa. 1) Freeze-dried root extract decreased SGOT, SGPT, and malondialdehyde [MDA] levels caused
by hepatotoxicity from acetaminophen (PO in mice). The decrease in glutathione and
cytochrome P450 in the liver caused by acetaminophen was reduced by burdock extract.1404
Either 300 mg/kg burdock root water extract or saline were given, or toxic injections of 800
mg/kg acetaminophen with or without the burdock extract were administered (PO in rats). The
acetaminophen-only group had significantly increased plasma transaminases and alkaline
phosphatase, along with liver DNA fragmentation, compared to controls and the acetaminophen
with burdock extract group. Addition of the burdock extract significantly reduced the elevated
liver MDA content caused by acetaminophen, as well as decreasing histopathologic evidence of
acetaminophen liver toxicity.3540
+ 2) The freeze-dried 4:1 water extract of the roots given at 900 mg/day after 3 weeks of 4 g
ethanol daily and continued for another 7 days with the alcohol led to significant improvement in
the hepatotoxicity after 1 day and 7 days as expressed by reduced levels of SGOT and SGPT,
triglycerides, and malondialdehyde when compared to alcohol alone (PO in rats) Pathological
changes in liver cell structure also improved when the extract was combined with the ethanol.3158
+ 3) The prior oral use of a chloroform extract of burdock roots at doses of 10, 30 or 100 mg/kg
significantly reduced stomach ulcers induced by ethanol by 61%, 70%, and 76%, respectively
(PO in rats). The extract given for 7 days at 100 mg/kg decreased stomach ulcers induced by
chronic acetic acid by 52%. Stomach acid secretion was reduced dose-dependently by the extract
when given intraduodenally. Gastric motility was unaffected. The extract demonstrated free
radical-scavenging ability in vitro.3541
CALAMUS p. 81
*Acorus calamus roots/rhizome
IIa. + 1) When vincristine was given IP for 10 consecutive days to induce neuropathic pain, a 50%
ethanolic extact of the dried rhizome was given in doses of 100 and 200 mg/kg 1 hour before the
vincristine and for an additional 4 days, and compared with saline and vincristine, vincristine-
only, and calamus-only controls in attenuating thermal and mechanical pain responses (PO in
rats). Vincristince-induced pain was accompanied with rises in tissue myeloperoxidase,
superoxide anion, total calcium, and histological changes, but the extract attenuated the pain and
these changes in a dose-dependent manner. The prevention of pain was thereby associated with
anti-inflammatory, antioxidative, neuroprotective and calcium inhibitory effects.3375
20
CANNABIS p. 83
*Cannabis sativa or Cannabis indica leaves and tops
Contraindications
I. 2) Do not use in personal or family history of schizophrenia (empirical).2,627,629
Cannabis use increases the risk of incidence of psychotic symptoms in the young with stronger
effects in those predisposed to psychosis,3275,3545 increases the risk of developing schizophrenia
and psychotic outcomes,3272-3274 and contributes to a poor prognosis for those with established
psychotic disorder (IH in human studies).3272,3545 The risks increase dose-dependently3273,3274 and
with frequency of use (human studies).3273
3) Avoid prolonged use of smoking cannabis, since this contributes to respiratory tract
inflammatory conditions (IH human studies)2,627,628,629,3275 and cardiovascular disease, possibly
precipitating acute coronary syndrome (IH human studies).3275,3277 Prolonged consumption by
some may cause psychological dependance (empirical, IH in human studies),628,1198,3275 and
physical withdrawal (IH in human studies).2,628,1198,3271
HOWEVER, even with high doses over prolonged periods, withdrawal sympotoms are mild
and the risk of dependency is low when compared to tobacco, alcohol, opioids, and
benzodiazepines (human studies).3271
4) Avoid motor vehicle operation, since driving ability can be impaired for up to 8 hours (IH in
human studies).2,627,268,629
Driving under the influence of cannabis heightens the risk of motor vehicle accidents dose-
dependently, increasing with higher frequency of use (human studies).3275,3276
Drug Interactions
Ib. 1) [NOTE: The order of this information has been reversed.] Concurrent abuse of cannabis and
other substances is not uncommon (empirical)628 and results in greater intoxication and
impairment when it is combined with opiates, ethanol, or barbiturates (IH in human
studies).1076,1077
Cannabis use is more common among those prescribed chronic opioid therapy (human
studies).2746 Those who are dependent on codeine are more likely to use cannabis than
nondependent regular codeine users [23% vs. 5%, respectively] and to use codeine for its
pleasurable effects, to relax, or to prevent withdrawal (human study).2747
HOWEVER, cannabis has been used to ease withdrawal from alcohol and opiates
(empirical).3270,3545 A 35-year-old man with HIV-related peripheral neuropathy likewise tried
multiple medicines for pain, using 360 mg/day of long-acting morphine plus 75 mg 4 times daily
of morphine sulphate for breakthrough pain; after using 3-4 puffs of cannabis 3-4 times daily,
morphine dosage decreased to 180 mg/day over 4 months and was discontinued after 9
months.2745 Cannabidiol, a nonpsychotropic component of cannabis, was found to inhibit cue-
induced heroin seeking in doses from 5-20 mg/kg (IP in rats). This was associated with
normalization of mesolimbic cannabinoid type-1 and glutamine R1 receptor expressions.2973
Ia. 1) Vomiting induced by cancer chemotherapy agents was relieved by cannabis in 78% of the
patients (IH in human clinical study).1078
In a randomized, double-blind, crossover trial, when 15 osteogenic sarcoma patients on high-dose
methotrexatechemotherapy used oral 10 mg/m2 THC 5 times daily and smoked THC in cannabis
after initial vomiting episodes, 14/15 responded and nausea and vomiting were signicantly
reduced compared to using placebo and cannabis with no THC (PO and IH in human clinical
study). The incidence nausea and vomiting diminished with increasing plasma THC
concentrations.2942 In 14 controlled trials with 681cancer patients using THC for chemotherapy-
induced vomiting, THC was as, or more, effective than standard antiemetic drugs (PO in human
clinical trials) . In addition, 2 controlled studies showed THC retarded chronic weight loss and
stimulated appetite in patients with advanced cancers, and 2 other controlled studies with 46
21
patients showed THC in doses of 10-20 mg was effective for cancerous pains (PO in human
clinical studies).2944
HOWEVER, in another trial with the same protocol for oral THC or smoked after a vomiting
episode, for 8 cancer patients taking adriamycin and cytoxan only 3/8 had a reduction of nausea
and/or vomiting (PO and IH in human clinical study).2943 A comparative study with 20 cancer
patients using oral THC and smoked cannabis for chemotherapy-induced vomiting found efficacy
in only 5; overall, 7 preferred THC, 4 preferred cannabis, and 9 had no preference (PO vs IH in
human clinical study). Perceptual distortions occurred in 7 including 4 with THC, 2 with
cannabis, and 1 with both.2944
+ 2) In 125 patients with peripheral neuropathic pain who remained on stable analgesia including
86 on opioids [15 on the stronger morphine, methadone, oxycodone, or pethidine and 71 on
the weaker tramadol, codeine, dihydrocodeine, and dextropropoxyphene] as well as 41 on
non-opioid analgesics or anti-inflammatory drugs, those who received a standardized cannabis
extract oromucosal spray with equivalent amounts of THC and cannabidiol for 5 weeks had
significantly reduced pain intensity and better sleep than those on placebo (human clinical study).
The cannabis group also had greater sedation and GI side effects, and 18% withdrew compared to
3% placebo withdrawals. Extending the study to 1 year maintained pain relief without increased
dose or toxicity.2748 In a crossover trial with 21 neuropathic pain patients, 25 mg of cannabis with
9.4% THC 3 times daily for 5 days compared to cannabis with 0% THC significantly improved
average daily pain intensity and sleep; routine medications continued by the patients included
opioids by 61%, antidepressants by 52%, anticonvulsants by 43%, and NSAIDs by 43% (IH in
human clinical study). Though mild, adverse effects were more frequent with the higher THC
dose.2940 States that have enacted medical cannabis laws have shown on average a 24.8% lower
annual opioid overdose mortality rate from 1999-2010.3404
+ 3) The 28 patients with distal sensory polyneuropathy as an expression of HIV neuropathic
pain who completed a randomised crossover trial using cannabis for 1 week (IH in human
clinical study) maintained the use of pain-modifying agents including 18 on opioids, 18 taking
anticonvulsants, 10 who used acetaminophen or NSAIDs, and 8 on tricyclic antidepressants.
Additional pain relief in daily functioning was significantly greater with cannabis than with a
placebo without THC. Changes in morphine equivalent doses and pain severity did not differ
between those who used concomitant opioids and those who did not. Changes in aspirin
equivalents were minimal.2848 In 50 HIV patients with chronic painful sensory neuropathy who
were randomly assigned to smoke cannabis or an identical placebo 3 times daily for 5 days, the
cannabis group had a significantly greater 34% reduction in daily pain, with 52% having over
30% reduced pain compared to 24% with this effect while using placebo (IH in human clinical
study). About half used concomitant medications divided similarly between gabapentin, opioids,
and others. Experimentally induced hyperalgesia from topical capsaicin application was also
significantly reduced in those subjects smoking cannabis.2847
+ 4) Vaporized cannabis extract given for 3 2/3 days to 21 patients using opioids for chronic pain,
including 11 taking morphine and 10 using oxycodone, significantly reduced pain by an average
of 27% without significantly altering plasma opioid levels (IH in human clinical study).3126
Of 30 chronic pain patients in a pain management center who used 1-5 grams [avg. 2.5 gr]
medical cannabis daily for 1-5 years, 93% reported moderate or greater pain relief, and no serious
adverse effects were noted (IH in human case series). Of those with adverse effects 70% were
able to decrease the medications such as opiates and NSAIDs that were causing the side
effects.2750 Cannabis has been shown effective for chronic pain by increasing analgesia when used
in combination with morphine (IH in human case series). A 47-year-old woman with chronic
multiple sclerosis had inadequate relief from a plethora of medications, including 75 mg/day of
long-acting morphine, but with the addition of 2-4 puffs of cannabis at bedtime she was able to
reduce her medications and adequately control her pain with 45 mg/day of morphine. Also, a 35-
year-old man with HIV-related peripheral neuropathy likewise tried multiple medicines for pain,
22
using 360 mg/day of long-acting morphine plus 75 mg 4 times daily of morphine sulphate for
breakthrough pain; after using 3-4 puffs of cannabis 3-4 times daily, morphine dosage decreased
to 180 mg/day over 4 months and was discontinued after 9 months. Finally, a 44-year-old man
with a lumbar spine injury had low back and leg pain resistant to physiotherapy and several pain
medications; he relied on 150 mg/day of long-acting morphine. Smoking cannabis 4-5 times daily
for 2 weeks allowed a decrease in morphine to 90 mg/day, then to 60 mg/day after 2 more weeks,
after which he was able to resume work with good pain control.2745 States that have enacted
medical cannabis laws have shown on average a 24.8% lower annual opioid overdose mortality
rate from 1999-2010.3404
In postoperative pain in 65 patients following analgesia with morphine, the use of an extract of
cannabis with 1 part THC to 0.3 parts cannabidiol, doses of 10 mg or 15 mg doses of the extract
led to pain relief reflected by rescue analgesia requirements similar to many analgesics routinely
used; sedation increased with increasing doses (PO in human clinical study).2749
+ 5) A group of 30 multiple sclerosis patients, 60% using the antispacity agents baclofen and
tizanidine and 7% taking the disease modifying drugs interferon beta-1a,b or glatiramer had
significantly reduced spasticity and pain compared to placebo after treatment with 800 mg
smoked once daily for 3 days in a placebo-controlled crossover trial (IH in human clinical
study).3305
Another 135 multiple sclerosis patients were randomly treated for overactive bladder with a
standardized cannabis extract oromucosal spray or placebo for 8 weeks in addition to a stable
dose of anticholinergics (PO in human clinical study). The dose was individually triturated and
found significantly effective for several secondary treatment endpoints including improvements
in nocturia, daytime voids, number of voids per day, and patient global impression of change. The
tolerance of the cannabis extract was good with the most common adverse effects related to the
central nervous system including dizziness [18%], headache [6%], disorientation [6%],
dissociation [6%], impaired balance [5%], and paresthesia [3%].2751
CARAWAY p. 84
Carum carvi seeds
Drug Interactions
II. 1) A butanolic fraction of the seed increased plasma levels and bioavailability of the
antitubercular drugs rifampicin, pyrazinamide, and isoniazide due to increased absorption from
enhanced permeation (PO in rats). A 40% reduced dose of these drugs combined with the fraction
was equivalent in bioavailability to a normal dose.3477
CASSIA p. 86
Cinnamomum cassia = Cinnamomum aromaticum bark
Drug Interactions
Ia. 1) In type 2 diabetes using the sulfonylurea drug glibenclamide, cassia further reduced fasting
glucose (PO in human clinical study).1592 A cassia extract also significantly reduced serum
glucose in type 2 diabetics with poor glycemic control taking oral hypoglycemics including
sulfonylureas and metformin or both (PO in human clinical study).1900
In a randomized, double-blind study of 66 patients with type 2 diabetes, along with taking the
sulfonylurea drug gliclazide for 3 months 23 were also given cassia extract at 120 mg/day, 23
received the extract at 360 mg/day, and 20 took a placebo, as changes from baseline for fasting
blood glucose and glycosylated hemoglobin [HbA1C] were compared (PO in human clinical
study). Each 120 mg of extract was derived from the water-soluble fraction of 4.8 grams of cassia
cinnamon. After 3 months, significant improvements for both parameters were shown in the low-
and high-dose groups, but not for the placebo group. The blood sugar and HbA1C reductions were
greater in the high-dose group, but only the low-dose group had a significant reduction in
23
triglyceride levels as well. Only the placebo group had a significant elevations of cholesterol and
the liver enzyme alanine aminotransferase.3244
In another study of 58 patients with poorly controlled type 2 diabetes, 30 given 2 grams of
cassia cinnamon powder daily for 12 weeks had significantly improved mean HbA1c and systolic
and diastolic blood pressures, compared to the 28 placebo controls (PO in human clinical study).
In addition, the fasting plasma glucose, waist circumference, and body mass index were improved
from baseline in the cassia group, of whom 24 treated were treated with metformin, 2 with
sulfonylureas, and 4 with both.2758
Tests of 2 extracts rich in B-type procyanidin oligomers derived from cassia from 2 different
areas of China were both found to be as effective as metformin in reducing extracellular glucose
in normal or insulin-resistant HepG2 cells (in vitro) and blood glucose in STZ-diabetic animals
(PO in rats).2836
III. + 3) Due to the depression of glutathione levels by cinnamaldehyde (in rats), the oral use of cassia
oil should be avoided with concurrent use of acetaminophen (paracetamol).400
CAT’S CLAW p. 89
Uncaria tomentosa bark or root
Drug Interactions
Ib. 1) A woman with cirrhosis from hepatitis C infection who was HIV positive was receiving
protease inhibitor treatment with atazanavir, ritonavir and saquinavir while she was also taking
a cat's claw preparation (PO in human case report). After taking the cat's claw for 2 months, it
was discovered in preparation for liver transplantion that her serum trough concentrations of all 3
protease inhibitors where greatly elevated above the therapeutic cut-off values. When the cat's
claw was withdraw, the serum trough concentration dropped dramatically to near normal
ranges.3520
II. 1) When cat's claw dried bark containing pentacyclic oxindole alkaloids was given at doses of
3.5 and 7.1 mg/kg, comparable to normal human doses, together with diazepam, both doses over
a span of 30 minutes enhanced the drug's reduction of spontaneous motor activity. The lower
dose also further increased diazepam's inhibition of exploratory ability but reduced diazepam's
musculoskeletal relaxanat activity (PO in mice).3519
IIa. + 2) After treatment with daily intraperitoneal injections of doxorubicin over 3 days to induce
leukopenia, a water extract of the inner and outer bark was given for 16 consecutive days (PO in
rats). The animals receiving the extract recovered significantly sooner than controls; those given
80 mg/kg extract daily showed normalized white blood cell counts after 10 days and those given
40 mg/kg had normal white counts after 15 days, but it took 20 days to return to normal for those
receiving only the doxorubicin. The increase in white blood cell counts included both
lymphocytic and neutrophilic cell fractions, whereas the positive control Neupogen® increased
only the non-lymphocyte fractions.3331
CAYENNE p. 90
*Capsicum frutescens fruit
Contraindications
I. 7) Avoid local application to areas of skin damage (empirical)401 that may result in an open sore
(empirical). 6,17,150
The application of 0.1% capsaicin cream for 48 hours to 20 subjects, compared to placebo in 12,
resulted in a maximal loss of sensory function by day 6 and autonomic function by day 16
including sudomotor, vasomotor, pilomotor functions and significant loss of nerve fiber densities
(TP in human study). nerve regeneration occurred within 40-50 days for autonomic nerves but 140-
150 days for sensory nerve fibers. Caution should be taken in using capsaicin on skin at risk for
ulceration, especially neuropathic conditions.2939
24
Drug Interactions
Ib. 2) Antacids are antagonized and the alimentary mucosa is further irritated (empirical).777
HOWEVER, a study of 50 consecutive patients with dueodenal ulcers proved by endoscopy
who were all being treated with a liquid antacid [containing 61 g/L aluminum hydroxide and 20
g/L magnesium hydroxide] 6 times daily, administered 1 g cayenne powder 3 times daily with the
standard meals to half of them (PO in human clinical study). There were no differences in
symptomatic relief and 80% of the ulcers healed in each group. No hemorrhage or erosions were
shown on endoscopy in the cayenne group, though 2 of the 25 had a mild intolerance to the
cayenne.3544
II. 4) The pungent component capsaicin was given at 3, 8, or 25 mg/kg daily for 7 days, when on
day 7 a single 80 mg/kg dose of the CYP 3A4 substrate simvastatin was given orally (PO in
rats). Compared to controls, the capsaicin led to a significant dose-dependent decrease of the
bioavailability of cholesterol-lowering simvastatin by 67%-78%. Likewise, the maximum plasma
concentration of simvastatin and its acid metabolite were also significantly reduced with
capsaicin pretreatment.3547
IIa. 1) The mineral absorption of calcium, iron, and zinc were all significantly improved with the
addition of 0.015g% of capsaicin to the diet, compared to the same diet without capsaicin (PO in
rats). Calcium absorption was improved the most. Capsaicin increased the uptake of zinc better
than either piperine or ginger.3471
CELANDINE p. 92
*Chelidonium majus root and herb
Contraindications
I. 4) Do not consume following an idiosyncratic hepatotoxicity after using celandine
(empirical).1890
Liver-specific CIOMS analysis of 33 hepatotoxicity cases in Germany associated with
celandine found 2 highly probable, 6 probable, 10 possible, 1 unlikely, and 3 excluded (PO in
human cases). The celandine hepatotoxicity cases had patient averages of 56 years of age, use for
36 days, latency until first symptoms of 30 days, and jaundice after 36 days, with a female
predominance.3304
CHAGA NEW
^ (Inonotus obliquus) mushroom
IIa. 1) An aqueous extract of the fruiting body was freeze-dried and given at a dose of 10 mg daily
for 24 days after immunosuppression induced by the chemotherapy drug cyclophosphamide
(PO in mice). By as early as 8 days after extract treatment, the number of granulocyte and
macrophage colony-forming units were almost to the level of non-immunosuppressed controls.
Serum levels of interleukin-6 were highly increased by the extract, and tumor necrosis factor-
was maintained at a background level, compared to its elevation in controls after the drug
treatment.3504
CHAMOMILE p. 94
Matricaria recutita = Matricaria chamomilla herb or flowers
Contraindications
II. 1) [Clarification] ALSO, REGULAR internal consumption should be avoided THROUGHOUT
pregnancy. A study of 392 pregnant Italian women found that those 37 who were regular users
of chamomile had a 21.6% higher frequency of threatened miscarriages, mostly in the 4th-5th
25
month of gestation, and a 21.6% increase in preterm labors compared to non-users (PO in human
study).3078
HOWEVER, the authors failed to identify by scientific name whether the chamomile used was
German (Matricaria recutita) or Roman (Chamaemelum nobile) chamomile.3078 Likewise,
scientific species identification was not utilized in describing the association of regular
chamomile use in 56 subjects for 3 to 9 months during pregnancy with low birth weight, though
the risk did not reach statistical significance (PO in human study). There was no association in
this study with chamomile use and preterm birth.3205
Ia. 1) A flower extract as a mouth rinse effectively treated oral mucositis from chemotherapy in 78
cancer patients (TP in human clinical study) .2541
A major constituent of chamomile, bisabololoxide A, was shown at a 10 mcM concentration
to enhance the antiproliferative effects of 3-10 mcM concentrations of 5-fluorouracil on human
leukemia K562 cells (in vitro).2863
IIa. + 2) Chamomile hydroalcoholic extract, given at 25 mg/kg for 4 days before and with IV cisplatin
before an SC formalin injection, reduced the second phase neuropathic pain expressions from
cisplatin-induced peripheral neuropathy (IP in mice). The chamomile extract given alone reduced
the first and second phase formalin-exacerbated pain better than morphine; the pain increased in
the first and second phase when cisplatin was given alone (IP in mice).3374
CHILI NEW
^ * Capsicum anuum fruit
["Peppers" refers to nonpungent varieties of this species eaten as vegetables; chilis are pungent.]
(chili pepper, Thai chili; Sp.: chile; Mex.: chilli)
Contraindications
I. 1) Do not use in chronic irritable bowel,24,777 due to neural irritant and intestinal contractile
properties of capsaicin (in vitro, animal, and human studies).176
2) Avoid use with allergic hypersensitivity, since this may result in urticaria (empirical).17
Drug Interactions
Ia. 1) Intestinal absorption of iron (ferrous sulfate) as part of fortified fish sauce with vegetables
and rice was reduced 38% when it was taken with 4.3 g chili pepper with 25 mg polyphenols (PO
in human study). This chili did not affect gastric acid secretion.2807
HOWEVER, the absorption of iron was significantly improved with the addition of capsaicin
to the diet, compared to the same diet without capsaicin (PO in rats).3471 No effect on iron
absorption was found when 0.5 g turmeric (Curcuma longa) with 50 mg of polyphenols was
taken instead.2807
Ia. 1) A dose of 20 gm of powdered dry fruit (containing 9.56 mg capsaicin, a concentration of 478
ppm) reduced stomach damage to the mucous membrane in 18 subjects when taken half an hour
before aspirin (PO in human study).211 Dilute capsaicin at 0.1 mcg/kg protected the stomach
from mucosal damage by aspirin (PO in rats).1120
HOWEVER, capsaicin at 1.0 mg/kg initially protected but then enhanced aspirin stomach
mucosal damage. At 10-30 mg/kg capsaicin aggravated the damage caused by aspirin (PO in
rats).1120
IIa. 1) A significant dose-dependent prevention of stomach ulcers induced by ethanol and acid was
shown by giving 3-30 mg/kg of capsaicin, probably due to increase mucosal blood flow and
reduced motility (PO in rats).522 Red pepper as 3.0%, and capsaicin as 0.01%, of the diet for 8
weeks followed by an acute exposure to ethanol showed gastroprotective effects by significantly
increasing activity of the endogenous antioxidant enzymes superoxide dismutase, glutathione
reductase, and glutathion-S-transferase in the stomach and intestinal mucosa and increasing
mucin content in stomach mucosa, compared to having no exposure to the spice (PO in rats).3347
26
Dilute capsaicin at 0.1 mcg/kg protected the stomach from mucosal damage by ethanol (PO in
rats).1120
HOWEVER, at 10-30 mg/kg capsaicin aggravated the damage caused by ethanol (PO in
rats).1120
2) The mineral absorption of calcium, iron, and zinc were all significantly improved with the
addition of capsaicin to the diet, compared to the same diet without capsaicin (PO in rats).
Calcium absorption was improved the most. Capsaicin increased the uptake of zinc better than
either piperine or ginger.3471
CHINESE HIBISCUS
Hibiscus rosa-sinensis flowers
(rose of China)
Contraindications
II. 1) Its excessive internal use should be avoided in early pregnancy (speculative),2 due to its
emmenogogue effects (empirical). [Plant part not identified for abortifacient use.]74
CHINESE RHUBARB p. 99
*Rheum officinale, *Rheum palmatum root
Drug Interactions
II. 1) A decoction of R. palmatum root of 2 g/kg administered in either a single dose or 7 doses with
200 mg/kg phenytoin after the last dose caused significant reductions in the peak serum
concentration and the bioavailability of phenytoin and its metabolites (PO in rats). The efflux of
phenytoin by P-gp in human colon cells was significantly increased, though MRP-2 phenytoin
transport from renal cells was inhibited (in vitro).3335
CHINESE SKULLCAP p. 100

Scutellaria baicalensis root
IIa. + 3) The hepatotoxicity effects of ethanol (alcohol) in conjunction with a 40% fat diet led to
elevated serum transaminase enzymes and LDH, as well as elevated triglyceride, LDL-
cholesterol, and total cholesterol that were all significantly reversed to near control levels when
100 mg/kg of water extract was given concurrently for 28 days (PO in mice).2839
CHOKEBERRY p. 101
Aronia melanocarpa fruit
Drug Interactions
Ib. 1) After his fourth cycle of trabectedin as second-line chemotherapy, a man with liposarcoma
suddenly developed weakness and diffuse muscle pain, after taking a chokeberry preparation
during the last course of trabectin and the subsequent 2 weeks (PO in human case report). Along
with increased serum levels of myoglobin, creatinine phosphokinase, and lactate dehydrogenase,
there was evidence of pancytopenia and a large increase in liver enzymes. After stopping the
chokeberry extract, the markers of myolysis slowly returned to normal and muscle strength
progressively recovered. Trabectedin is metabolized by CYP3A4. The evidence indicated that it
was probable the adverse event was an interaction of trabectedin and chokeberry, likely through
inhibition of CYP3A4 (speculative).3369
IIa. + 3) The antiarrhythmic drug amiodarone given intratracheally causes direct lung damage
resulting in acute toxic pneumonitis, inducing oxidative stress and fibrosis, but these effects and
pulmonary inflamation were significantly reduced with chokeberry juice given at 5 ml/kg for up
to 10 days after exposure to amiodarone (PO in rats).3436
27
CINCHONA p. 101
*Cinchona spp. bark
IIb. 1) The inhibition by quinine and/or quinidine of ethacrynic acid and 1,3-bis(2-chloroethyl)-1-
nitrosurea (BCNU or carmustine) phase II glutathione S-transferase conjugation by
[CORRECTION:] tumor cells (in vitro) could lead greater retention of these and increased
efficacy of BCNU as an agent against [CORRECTION:] some cancers (speculative).1547
CINNAMON p. 102
*Cinnamomum verum = Cinnamomum zeylanicum bark [See also Cassia.]
Drug Interactions
I. 1) The extract did not reduce normal blood glucose.1763 In a study of 37 type 2 diabetics taking
stable doses of metformin or gliclazide, those taking 3 gram/day of cinnamon had significantly
reduced fasting blood glucose, glycosylated hemoglobin, triglycerides, and weight compared to
baseline, but not compared to those taking placebo (PO in human clinical study).3287
III. + 3) Due to the depression of glutathione levels by cinnamaldehyde (in rats), the oral use of
cinnamon oil should be avoided with concurrent use of acetaminophen (paracetamol).400
CLOVE p. 103
Syzygium aromaticum = Eugenia caryophyllata buds
IIa. + 1) Pretreatment with 10 mg/kg of eugenol an hour before administration of a single 30 mg/kg
dose of indomethacin significantly reduced the indomethacin-induced formation of stomach
ulcers (PO in rats). This was accompanied by significant reductions in gastric acid and pepsin
activity, along with decreased gastric mucosal nitrite and malondialdehyde, and an increase in
reduced glutathione and mucin concentration, compared with indomethacin alone.2957
+ 2) Pretreatment with 10-100 mg/kg of eugenol an hour before administration of a single 1 ml
dose of ethanol significantly reduced the alcohol-induced formation of stomach ulcers both in
number and degree of damage (PO in rats).2958
COCOA p. 104
Theobroma cacao seed
Drug Interactions
III. + 2) Consumption of single doses of 300 ml cocoa containing 897 mg flavanols and 81 mg aspirin
alone and combined in a crossover trial with 16 subjects demonstrated that these two agents had
similar and additive effects inhibiting platelet function and inhibiting platelet activity shown by
P-selectin expression induced by collagen with epinephrine, but not collagen with ADP, after 2
and/or 6 hours (ex vivo).2906 When cocoa tablets with 234 mg flavanols and procyanidins were
taken daily for 28 days by 13 subjects, the P selectin expression and collagen- and ADP-induced
platelet aggregation was significantly reduced compared to the 15 in the placebo group (ex
vivo).1447
Ia. + 1) Cocoa that supplied 963 mg flavanols daily to patients with diabetes type 2 on oral
hypoglycemics, insulin, antiplatelet drugs, statins, beta-blockers, and/or ACE inhibitors
increased flow-mediated dilation (PO in human clinical study).2600
Twelve subjects with type 2 diabetes, 5 using the oral hypoglycemic metformin, 8 taking statins,
and 3 on antihypertensives, consumed daily for 8 weeks each with a 4-week washout 3
chocolate bars of 15 grams each with 16.6 mg epicatechins and 3 chocolate bars with > 2 mg
epicatechins; only the high epicatechin bars led to significantly increased HDL and lower ratio of
total cholesterol:HCL (PO in human clinical trial). The beneficial changes reverted to baseline
values when the high epicatechin chocolate intervention stopped. No changes in weight gain,
28
glycemic control, insulin resistance or the inflammatory marker C-reactive protein were noted
with either type of chocolate bar.2740
+ 2) In 20 patients with congestive heart failure, all of whom were taking beta-blockers and
ACE inhibitors or angiotensin receptor blockers and most of whom used diuretics, statins,
and oral anticoagulants the half who ate 40 g twice daily of a commercial dark chocolate with
70% cocoa [providing 1.25 g/day of total polyphenols] had significantly better flow-mediated
dilation in the brachial artery after 4 weeks than those taking placebo (PO in human clinical
study). This surrogate marker of vascular endothelial function is not improved by statins in
congestive heart failure patients. In addition, platelet adhesion was significantly reduced within
hours after the chocolate was consumed, but this effect was not sustained after the flavanols were
cleared from the blood overnight. Blood pressure, low on average at baseline at 110/66 mmHg
due to medication, was not significantly changed, nor were weight gain and blood lipids
altered.3077
COLA p. 109
Cola nitida, Cola acuminata seed
IIb. 1) The minimum concentration of fluoroquinolone antibiotic drugs ciprofloxacin, perfloxacin,
and levofloxacin necessary to inhibit the grow of Escherichia coli decreased as the ratio of cola
seed methanolic extract to drug increased to 3:2 for ciprofoxacin and 4:1 for perfloxacin and
levofloxacin (in vitro).3034
COPTIS p. 113
Coptis chinensis and Coptis groenlandica rhizomes
Contraindications
II. 1) Do not use in jaundice in newborns or from hemolytic anemia (speculative).1092
HOWEVER, when coptis rhizome and/or berberine-containing amur cork tree (Phellodendron
amurense) bark were given in herbal concoctions according to traditional dosage and indication
to 20 patients with chronic cytopenic hematological conditions, though 3 patients with
thalassemia intermedia had transient elevation of serum bilirubin, there was no associated
aggravation of anemia or liver dysfunction (PO in human clinical study).3108
Drug Interactions
Ia. 1) The combination of 1500 mg berberine daily for 3 months in 43 type 2 diabetes patients with
29
study).3238
Ia. + 3) When 500 mg berberine hydrochloride was given twice daily with simvastatin 20 mg once
daily of berberine derived from C. chinensis significantly lowered triglycerides, total cholesterol,
and LDL-cholesterol compared to 52 diabetics on placebo, along with significantly reducing the
fasting and postload plasma glucose, HbA1c, body weight and systolic blood pressure (PO in
human clinical study).2907
+ 4) When 500 mg berberine hydrochloride was given twice daily with simvastatin 20 mg once
berberine and/or 6 mg/kg/day simvastatin (PO in rats).2905
IIa. + 4) A methanolic extract of C. chinensis rhizome at doses of 100, 200, and 400 mg/kg and
berberine at 200 mg/kg given for 10 days with cocaine significantly inhibited the excessive
area with the coptis and berberine, indicating a reduction in the production of dopamine (PO in
rats). This suggests that coptis and berberine may help reduce the chronic cocaine psychological
dependence (speculative), since coptis rhizome has been used in the treatment of substance abuse
(empirical).2753
30
by doxorubicin.3148
CORN SILK NEW

^ Zea mays stigma
IIa. 1) The damage from acute kidney toxicity with the use of the antibiotic gentamicin was reduced
by 200 and 300 mg/kg of corn silk given 1 hour befor 100 mg/kg of gentamicin was injected
intraperitoneally daily for 8 days (IP in rats). Elevations in plasma creatinine by gentamicin was
significantly reduced by the corn silk, though increased urea was not. Histopathological damage
was somewhat decreased, as the corn silk reduced interstitial nephritis but not the acute tubular
necrosis or hyaline cast formation, compared to controls receiving only gentamicin.3486
IIb. 1). The major corn silk flavonoid maysin reduces the viability of PC-3 androgen-independent
prostate cancer cells in a concentration-dependent manner and at 50 mcg/ml acts synergistically
with the anti-cancer agents 5-fluorouracil, camptothecin, cisplatin, and etoposide to inhibit the
growth significantly more than the chemotherapy agents alone (in vitro).3488
CRANBERRY p. 117
Vaccinium macrocarpon fruit
Drug Interactions
Ib. 1) A report on 5 individuals suggested cranberry juice may increase the effects of warfarin (PO
in human case series).1764 In one of several other cases, a man taking warfarin with an INR of 2-3
prior to using 24 oz cranberry juice daily for 2 weeks developed blood in his sputum and stools,
low hemoglobin, and an INR of >18 (PO in human case report).2505
HOWEVER, when 30 patients on warfarin with stable INRs of 1.7-3.3 were randomized to
240 ml cranberry juice cocktail or matching placebo daily for 2 weeks, there was no resulting
differences between groups in plasma R- or S-warfarin concentrations (PO in human clinical
trial). The only significant difference between groups in mean INRs measured every 3 days was
on day 12, when the cranberry group INR value was higher, but by day 15 the groups values were
equivalent.2763 The juice of only 1 of 5 commercial cranberry juice samples tested showed
significant inhibitory effects on metabolism of warfarin by CYP2C9 (in vitro). When 16 healthy
volunteers consumed the inhibitory cranberry juice prior to a single dose of warfarin, its
bioavailability and its half-life were not increased (PO in human study). The inhibition (in vitro)
did not correlate with warfarin clearance (in vivo), since warfarin metabolism in the liver of living
subjects is remote from the site of exposure to the inhibitory cranberry components in the
intestines.3083
31
Ia. 1) Fifteen patients with diabetes type 2 taking oral hypoglycemics were shown to have
decreased total cholesterol and LDL-cholesterol when taking 500 mg capsules of cranberry
extract 3 times daily after meals for 12 weeks compared to 15 using placebo (PO in human
clinical study).3098
IIa. 1) Cranberry extract at 100 mg/kg daily for 10 days reduced the cardiotoxicity of a single 15
mg/kg IP dose of doxorubicin given on the seventh day (PO in rats). The antioxidant extract
reduced mortality and ECG changes, while inhibiting glutathione depletion, oxidized glutathione
and malondialdehyde accumulation, and elevation of myeloperoxidase and lactose
dehydrogenase, among other improvements to doxorubicin cardiotoxic effects.3080
CRUCIFERS p. 120
Brassica spp. heads or leaves
IIa. + 1) The glucosinolate hydrolysis product indole-3-carbinol from cruciferous vegetables protected
against hepatotoxicity from the antitumor drug trabectidin when given at 0.5% of the diet for 6
days prior, but it did not interfere with trabectidin's antitumor efficacy (PO in rats). A dietary
concentration of only 0.1% indole-3-carbinol was not protective, nor was 0.2% of its acid
condensation product, diindolylmethane.2177
2) The isothiocyanate sulfurophane, derived mostly from broccoli sprouts, reduced
hepatotoxicity activities induced by cisplatin when sulforaphane was given at 500 mcg/kg daily
for 3 days prior to the cisplatin (IP in rats). The reduced damage was a result of protection of liver
mitochondrial function and antioxidant enzymes and prevention of oxidative stress.2934
DAN SHEN
Salvia miltiorrhiza root p. 122
Drug Interactions
Ia. + 1) The bioavailability and maximum plasma concentration of drug fexofenadine were reduced
by 37.2% and 27.4%, respectively, following consumption of 3 g daily of dan shen extract for 10
days by 12 healthy men; the average clearance of fexofenadine was increased by 104.9% (PO in
human study). This effect was due to induction of P-glycoprotein mRNA by deterpenoid
components of dan shen, specifically cryptotanshinone and tanshinone IIA (in vitro).3424
+ 2) Though a single 1g dose of dan shen extract led to an 87% increase in maximum plasma
concentration of midazolam after 1 dose of the drug, when 3 g of the extract was given daily for
10 days it decreased the maximum concentration of 1 dose of midazolam by 66.6%, half-life by
43.8%, and bioavailability by 79.9% in 12 healthy subjects (PO in human study).3425 Likewise,
when 12 men were given extracts of 12 g of dan shen for 14 days, midazolam oral clearance was
increased by 35.4% and the maximum concentration and bioavailability were decreased by
31.1% and 27.0%, respectively, but the half-life was not changed (PO in human study).3443
Testing the extract component diydrotanshinone I showed it inhibits CYP3A, while the dan
shen components cryptotanshinone and tanshinone IIA induce CYP3A (in vitro).3425
Ib. 1) The effect of anticoagulants404 can be increased, exemplified by warfarin (PO in human case
reports).202,444,715
Dan shen ethyl acetate extract with major tanshinones given at 2 g/kg for 3 days increased oral
warfarin steady state plasma concentration by 23% (PO in rats).3444
DOG ROSE p. 126

Rosa canina dried fruit (hips)
Ia. + 2) In 89 rheumatoid arthritis patients using acetaminophen, NSAIDs, steroids and disease-
modifying anti-rheumatic drugs including methotrexate, leflunomide, chloroquin, or other
32
biological antirheumatic drugs, those 44 taking 5 grams daily of rose-hip powder a significantly
better health assessment disability index after 6 months than those on placebo (PO in human
clinical study). The Physicians Global Scale and patient quality of life scores were also
significantly better in those on rose-hip than in the placebo group. The drug intake of both groups
did not differ at baseline or after 6 months.2962
DONG QUAI p. 127

Angelica sinensis root
Ib. + 1) Among 31,938 Chinese breast cancer survivors who were treated with tamoxifen, almost
half also used dong quai. The hazard ratio for subsequently developing endometrial cancer in the
157 cases that occurred was reduced significantly by dong quai use (PO in human population
study).3517
IIa. + 4) Equal quantities of astragalus root (Astragalus membranaceus) and dong quai root were
extracted with ethanol and water, the extracts combined, and 2.1 grams daily given with or
without the ACE inhibitor enalapril to monitor kidney fibrosis and compared to enalapril alone
(PO in rats). The tubulointerstitial fibrosis was reduced by the herbal extract and enalapril
separately along with transforming growth factor-1 [TGF-1], but the herbal-drug combination
had the greatest effect by significantly reducing TNF-, collagen accumulation, fibroblast
activation, tubular cell apoptosis more than enalapril alone.2728 A decoction of equal parts of the 2
roots given at the same dose was previously shown a decrease in TGF-1 puromucin-induced
nephrosis similar to enalapril (PO in rats),2729 while 3.6 g/kg daily dose of a 5:1 mixture of
astraglus and dong quai roots, respectively, as a decocted extract also modestly decreased kidney
TGF-1 mRNA expression following streptozotocin-induced damage, similar to the ACE
inhibitor benazepril (PO in rats).2730
ECHINACEA ANGUSTIFOLIA p. 129

Echinacea angustifolia roots
(Echinacea, narrow-leaved coneflower, combflower, Sampson root, black Sampson)
Contraindications
I. 1) Allergic hypersensitivity to plants in the Asteraceae family (empirical).777,1890
A man with a long history of asthma and hay fever developed hypereosinophilia and very
elevated IgE associated with abdominal cramps and occassional nausea and diarrhea for 3 years
that began and ended with supplementation of an uncharacterized echinacea supplement (PO in
human case report). Treatment with prednisone was finally able to be tapered off after he
discontinued the echinacea which was suspected of causing an IgE-mediated allergic response.2759
Complementary Adjunct
I. 1) In 26 adults of ages 38-79 years with respiratory disorders [chronic bronchitis, respiratory
insufficiency, and asthma] receiving an autumnal influenza vaccine for types A and B, 12 were
also given a standardized root extract for 1 month prior and for 2 months after the vaccination
(PO in human clinical study). One extract tablet was given twice daily for 15 days, once daily for
the next 15 days, then once every other day for 2 months. The hydroalcoholic extract tablet was
100 mg and was standardized to >2% echinacoside, >5% branched galacturonic polysaccharide,
and <0.1% alkamides. The number of upper respiratory viral infections that occurred from the
time of the vaccination until 4 months afterward was 5 including 3 with respiratory complications
in those receiving only the vaccine, while those receiving the extract with the vaccine had only 1
viral respiratory infection with no complications. In 12 others receiving only the extract, 2
respiratory viral infections occurred including 1 with respiratory complications; the total
leucocyte count, lymphocyte percentage, and IgG antibody levels all statistically increased in this
group between baseline and day 105.3178
33
ECHINACEA PALLIDA p. 132
Echinacea pallida root or whole plant
Contraindications
IIb. + 1) The 52% ethanolic extract of the whole plant given in water at a 10% concentration reduced
kidney damage and weight loss caused by the chemotherapy drug cisplatin (PO in mice). This
effect was due in part to restoring oxygen consumption in the kidneys.2726
ECHINACEA PURPUREA p. 134

Echinacea purpurea aerial plant or whole plant
Contraindications
Drug Interactions
Ia. + 1) E. purpurea whole fresh plant 8:1 extract, standardized to 0.25 mg/ml alkamides, 2.5 mg/ml
cichoric acid and 25.5 mg/ml polysaccharides, was given in 250 mg doses 3 times daily for 28
days to 16 healthy subjects taking lopinanavir-ritonavir for the first 14 days (PO in human study).
After these 14 days, there was no change in lopinavir bioavailability or peak concentration. After
the extract was given 28 days, a single dose of fexofenadine and one dose of midazolam were
then administered, and the midazolam bioavailability was significantly reduced as its clearance
was increased. The fexofenadine pharmacokinetics were not significantly altered. This extract
was therefore found to have a modest inducing effect on CYP 3A as shown with midazolam, but
not enough to counter the CYP 3A inhibiting effect of ritonavir. It had no effect on Pgp activity
as it applies to fexofenadine.3099
HOWEVER, when 800 mg of the whole plant extract was given twice daily for 28 days in
another study, it had no significant effect on midazolam bioavailability (PO in human study).1589
Based on clinical relevance, the pharmacokinetic interaction risk has been assessed as low
(speculative).3222
Ia. + 3) The dried juice dose of 500 mg daily together with10 mg zinc, 15 mcg selenium and 50 mg
vitamin C given to 37 chronic obstructive pulmonary disease [COPD] patients with acute upper
respiratory tract infections treated with ciprofloxacin helped to lessen and shorten exacerbations
compared with 32 given placebo, in a double-blind, randomized study of mostly male patients
with a mean age of 66 years (PO in clinical study).2796
HOWEVER, the dried juice alone at 500 mg/day did not differ from placebo when combined
with ciprofloxacin in treating upper respiratory tract infections in 36 subjects with COPD (PO in
IIa. + 1) A water-soluble polysaccharide complex from this species increased both the antitumor and
the antimetastatic effects of cyclophosphamide in transplanted lung carcinoma (in mice).2809
34
HOWEVER, the tincture of this species, though it did not influence cytostatic therapy or
change metastasis, did stimulate lung carcinoma tumor growth (in mice).2809
ECHINACEA PURPUREA root p. 136
Contraindications
II. 4) Echinacea purpurea root use should be avoided in AIDS and HIV infection (speculative).4,17
HOWEVER, in a 15-day open-label trail with 15 HIV patients receiving anti-retroviral
treatment with darunavir/ritonavir, 500 mg of the root extract given every 6 hours for 14 days was
well tolerated and did not significantly affect the drug pharmacokinetics (PO in human clinical
study).2793
Drug Interactions
Ia. 1) Echinacea purpurea root extract at 1.6 g daily for 8 days reduced overall bioavailability of IV
midazolam in 12 subjects (PO in human study).1588
HOWEVER, when 15 HIV patients took 500 mg of the root extract every 6 hours for 14 days,
the extract did not significantly affect the bioavailability or activity in the group of an oral
combination of the CYP 3A4 protease inhibitor substrates darunavir and ritonavir, though a few
individuals showed up to 30% less bioavailability for darunavir while a couple showed more (PO
in human clinical study).2793 Likewise, the metabolism of CYP 3A4 protease inhibitor substrate
etravirine was not significantly impacted by 1500 mg of the root extract daily for 14 days in 15
HIV-infected patients.3538 Based on clinical relevance, the pharmacokinetic interaction risk has
been assessed as low (speculative).3222
IIa. + 1) A water-soluble polysaccharide complex from this species increased both the antitumor and
the antimetastatic effects of cyclophosphamide in transplanted lung carcinoma (in mice).2809
HOWEVER, the tincture of this species, though it did not influence cytostatic therapy or
change metastasis, did stimulate lung carcinoma tumor growth (in mice).2809
ELEUTHERO p. 140
Eleutherococcus senticosus syn. Acanthopanax senticosus root
Drug Interactions
III. 2) Eleuthero association with falsely elevated digoxin levels in the absence of toxic effects was
presumably due to a digoxin assay interaction (ex vivo in human case report).907
A new analyzer technology from Abbott Laboratories has led to development of 2 analyzers,
iDig and cDig, using specific monoclonal antibody against digoxin for which "Siberian ginseng"
does not interfere with detection of digoxin (in vitro).3435
ENGLISH LAVENDER p. 141

Lavandula officinalis syn. Lavandula angustifolia syn. Lavandula vera flowers
Ia. + 2) In randomized, placebo-controlled, double-blind study of 100 patients of ages 19-64 years
with renal colic, half were given 75 mg IM of the NSAID dicofenac, while the other 50 were the
same diclofenac treatment combined with aromatherapy with 2% lavender oil (IH in human
clinical study). Using a visual analogue scale to assess pain severity, after 30 minutes the
combined treatment of the drug with lavender oil inhalation provided significantly greater relief
from pain than did the drug alone, especially among female patients.3533
35
ENGLISH PLANTAIN p. 142
Plantago lanceolata leaves
IIa. + 1) An aqueous extract was shown to significantly reduce the score for stomach ulcers from
indomethacin better than the standard drug misoprostol at 280 mcg/kg when the extract was
given at 400 mg/kg (PO in mice).2838
+ 2) An aqueous extract was shown to significantly reduce the score for stomach ulcers from
cysteamine when the extract was given at 400 mg/kg, though not as well as the standard drug
ranitidine at 70 mg/kg (PO in mice).2838
EUCALYPTUS p. 146
*Eucalyptus spp. leaves
Drug Interactions
II. + 3) When eucalytus (E. globulus) dried leaf was given at doses of 3.25 and 6 mg/kg, comparable
to normal human doses, together with diazepam, both doses after 30 minutes inhibited the drug's
depressant mental effects and especially its musculoskeletal relaxanat activity (PO in mice).3519
EVENING PRIMROSE p. 148

Oenothera biennis seed oil
Ia. + 4) In a randomized study, 40 acne patients received isotretinoin treatment for 8 weeks, with or
without 2700 mg of evening primrose oil 3 times daily, providing 240 mg of gamma-liolenic
acid, to observe the effect on the isotretinoin adverse effect of xerotic cheilitis (PO in human
clinical study). After 8 weeks there was a significant reduction in transepidermal water loss of the
lips in the patients receiving EPO which improved the xerotic cheilitis.3478
FENUGREEK p. 151
Trigonella foenum-graecum seed
Drug Interactions
Ia. 1) Fenugreek hydroalcoholic extract, in type 2 diabetes patients using sulfonylureas or
biguanides, or both, significantly decreased HbA1c, lowered fasting and 2-hour postprandial
insulin levels, and increased insulin sensitivity, compared to placebo (PO in human clinical
study).1360
In 69 type 2 diabetic patients taking sulfonylureas, 46 were given 6 pills of fenugreek total
saponins 3 times daily for 12 weeks, while the others received placebos (PO in human clinical
study). The fenugreek group had significantly lower fasting and 2-hour postprandial blood
glucose, HbA1c, and clinical symptom scores, compared to controls.2815
Hypoglycemic activity was also shown in diabetes melitus type 2 with 100 grams defatted
seed powder for 10 days with 15 patients taking glyburide (glibenclamide), glipizide, and/or
metformin (PO in human clinical study).1645 In 10 type 2 diabetic patients on stable
glibenclamide using 25 grams of the powdered seeds daily for 15 days in a crossover design,
plasma glucose was significantly lower following an IV glucose tolerance test (PO in human
clinical study).130 In 21 patients taking 15 grams powdered seeds soaked in water, of whom 10
were using glibenclamide and metformin and 7 glibenclamide alone, postprandial levels were
significantly reduced (PO in human study).961 In 20 patients with mild cases of type 2 diabetes,
but not in 20 with severe cases, using 5 grams of fenugreek powder daily without oral
hypoglycemic drugs significantly reduced fasting and postprandial blood sugar after 1 month (PO
in human clinical study).339
36
Ia. + 1) In a placebo-controlled, double-blind study of 50 patients with Parkinson's disease, 600
mg/day of a standardized extract of fenugreek was given for 6 months as an adjuvant to L-dopa
(PO in human clinical study). The United Parkinson's Disease Rating Scale total score showed a
rise of 0.01%, compared to a 13.36% rise for placebo. In addition, scores of several other tests
were around 5 times better with the fenugreek extract than with placebo. Tolerability and safety
of the extract were excellent.3394
+ 2) In a randomized, placebo-controlled, double-blind study of 101 university students with
moderate to severe primary dysmenorrhea, 51 took 2-3 900 mg capsules of fenugreek 3 times
daily during the first 3 days of menstruation over 2 menstrual cycles (PO in human clinical
study). In addition to having significantly reduced menstrual pain severity and duration for both
cycles in comparison to placebo, the fenugreek group also used significantly fewer NSAID
tablets such as ibuprofen and mefenamic acid on average. The analgesics were taken an hour or
more after the fenugreek or placebo capsules and after recording the pain severity.3416
IIa. 1) A 1% aqueous extract of fenugreek seeds with ethanol for 60 days reduced hepatotoxicity
and brain damage compared to alcohol alone (PO in rats). 1484
After 30 days of 6 g/kg/day of alcohol alone, using 200 mg/kg/day of a 12.5-16.5:1
methanolic extract dissolved in water for another 30 days in addition to the ethanol led to
significant reductions in protein carbonyl content and lipid peroxidation products, increased
activity antioxidant enzymes, and restoration of thiol group levels compared to controls (PO in
rats). These effects were equivalent to the positive control: 100 mg/kg/day of silymarin.3156
FO-TI p. 156
Polygonum multiflorum = Reynoutria multiflora root
(Chinese knotweed; Ch: he shou wu)
Contraindications
I. 1) Avoid in diarrhea, due to its irritant properties (empirical)150
associated with its anthoquinone component emodin.3367
FRANKINCENSE p. 158
Boswellia serrata resin
Ia. 1) In osteoarthritis of the knee, those taking placebo used ibuprofen more than subjects using
100 mg/day of extract with 30% 3-O-acetyl-11-keto-beta-boswellic acid [AKBA], but outcomes
were significantly better in the extract group (PO in human clinical study).2483
A randomized, placebo-controlled, double-blind trial for 90 days with 60 knee osteoarthritis
patients using ibuprofen and 100 mg extract with 30% AKBA or 100 mg of 20% AKBA and oil
both had significantly less pain and stiffness than placebo, but the AKBA/oil group had a quicker
response and significantly better functional ability scores than placebo (PO in human clinical
study).2804
+ 2) In a randomized double-blind study of 44 brain tumor patients receiving radiotherapy for
several weeks, dexamethasone was used to control cerebral edema, but those also taking 4200
mg of H15 extract daily had significantly reduced brain swelling at therapy's end compared to
baseline than those using placebo (PO in human clinical study). The dexamethasone doses were
individualized, but the differences between the groups were not significant. Six patients in the
boswellia group, but none in the placebo group, had diarrhea. There were no differences in
quality of life or mental functioning between the 2 groups.2846
+ 3) In a randomized, placebo-controlled, double-blind study of 71 patients with diabetes type 2
treated with metformin but having fasting blood sugar levels of 140-200 mg/dl, 400 mg gum
resin capsules or placebo were given twice daily for 12 weeks (PO in human clinical study). The
37 patients given the gum resin had significantly lowered fasting blood sugar, glycosylated
37
hemoglobin, insulin, total cholesterol, LDL, and triglyceride levels compared with the 34 in the
placebo group, but no significant effects on liver and kidney function tests.3413
+ 4) Of 32 patients with asthma and stabilized on 1 inhalation twice daily of corticosteroids
(fluticasone + sameterol, beclomethasone + formoterol, or budesonide + formoterol), along
with long-acting oral beta-agonists, 18 were randomized to receive 4 weeks of additional
treatment with 500 mg/day of boswellia standardized extract in a phospholipid base and 14 did
not (PO in human clinical study). During the 4 weeks they could reduce the number of
corticosteroid inhalations and kept track of the total number. Compared to the 14 controls, the
number of inhalations was significantly lowered with the boswellia extract by 26% in week 2,
28% in week 3, and 42% in week 4. By week 4 the boswellia group were using on average 8
inhalations per week compared to 13.8 inhalations in the group without boswellia.3542
FRENCH MARITIME PINE p. 158

Pinus pinaster = Pinus maritima bark fraction
Ia. 1) The polyphenol fraction used in high blood pressure allowed significant reduction of
nifedipine dosage compared to placebo (PO in human clinical study).1623
Also, 150 mg/day Pycnogenol for 8 weeks compared to placebo significantly reduced the
capillary filtration leading to tissue edema associated with nifedipin used in the treatment of
hypertension in 30 patients (PO in human clinic study). Likewise, the capillary filtration
associated with ACE inhibitors in 23 patients was also significantly reduced by the same dose
after 8 weeks, compared to placebo.2794
2) Use of 150 mg of Pycnogenol daily for 3 months in osteoarthritis with concurrent NSAIDs
and/or analgesics led to a significant reduction in inflammation and pain scores and less drug use,
compared to baseline and placebo (PO in human clinical study).2324
Also, 150 mg/day of Pycnogenol for 3 months in a randomized, double-blind, placebo-
controlled trial with 37 knee osteoarthritis patients led to significantly reduced scores for total
symptoms, pain, and physical function at 60 and 90 days, while NSAIDs and COX-2 inhibitors
used were reduced significantly after 30, 60, and 90 days and placebo use increased significantly
after 90 days (PO in human clinical study).2795
+ 5) When 40 mg Pycnogenol with 70% procyanidins and 80 mg bilberry (Vaccinium myrtillus)
extract with 36% anthocyanins as a standardized combination was given once daily in the
morning to 79 ocular hypertension patients either alone or together with latanoprost eye drops
and compared to latanoprost alone, the extract combination with the drug was best for lowering
intraocular pressure and enhancing retinal blood flow (PO in human clinical study). The extract
alone eventually was similarly effective as the drug for lowering intraocular pressure, but it took
24 weeks for the extract compared to only 4 weeks with latanoprost. The only adverse effects
were those related to latanoprost.2966
+ 6) When given to 33 patients with allergic asthma, 100 mg daily of Pycnogenol for 6 months
decreased the daily dosage of the inhaled corticosteroid drug fluticasone propionate in 55%,
whereas just 6% of those 32 taking only the corticosteroid reduced the dosage (PO in human
clinical study). None of the Pycnogenol group increased fluticasone dosage, but 18.8% of the
other group did. In addition to reducing or maintaining the drug dose, asthma symptoms were
significantly reduced and breathing parameters significantly improved only in the Pycnogenol
group, while they also used less of the rescue medication salbutamol than those taking only
fluticasone.3093
In a randomized, placebo-controlled, double-blind 3-month study of 60 patients ages 6-18
years with childhood asthma, the half receiving Pycnogenol at 1 mg/lb of body weight daily,
along with the oral medication zafirlukast and the rescue inhalant albuterol, had significantly
better symptom relief and pulmonary function and significantly less albuterol use and urinary
38
leukotrienes after 1, 2, and 3 months than the half who took placebo with their medications (PO
+ 7) In a randomized, placebo-controlled, single-blind trial Pycnogenol mixed in a 50:50 solution
of glycerin and water was applied locally at 1 mg/kg/day 3 times daily for 1 week in children ages
6-15 years to oral mucositis induced by chemotherapy including mitoxantrone, chlorambucil
and prednisolone for non-Hodgkin lymphoma or other drugs for acute lymphoblastic leukemia
and acute myeloid leukemia; it significantly reduced the WHO grade of the mucositis for Grades
I to III, compared to those treated locally only with glycerin (TP in human clinical study). While
only 4.2% healed completely and 12.5% improved in the glycerin group, 58.3% healed
completely and 37.5% improved in the Pycnogenol in glycerin group.3333
GARLIC p. 161
Allium sativum cloves
Drug Interactions
Ia. 1) Two garlic caplets per day for 3 weeks in 10 healthy subjects reduced saquinavir by 49%-
54% compared to baseline (PO in human study).1210
When 600 mg garlic extract with 3.6 mg allicin was taken by 10 healthy males twice daily for
21 days, though it decreased the average saquinavir bioavailability by 15%, it did not change
bioavailability of CYP3A4 substrate simvastatin (PO in human study). The CYP3A4 expression
was reduced by only 4% in the liver and 13% in the duodenum, but intestinal P-glycoprotein
increased by 31%. So, since saquinavir is a substrate of both CYP3A4 and Pgp, the induction of
Pgp best explains the decreased saquinavir levels, in spite of less CYP3A4 metabolism.3223
+ 3) The use of 300 mg garlic tablets with 0.6% allicin 3 times daily together with metformin for
24 weeks by 30 patients with diabetes type 2 resulted in significantly lower levels of fasting blood
sugar, total cholesterol, LDL-cholesterol, and triglycerides compared to diabetics who took only
metformin (PO in human clinical study). HDL-c was significantly increased in the garlic group
after 12 weeks. No adverse effects were reported.3089
Based on clinical relevance, the pharmacokinetic interaction risk has been assessed as low
(speculative).3222
+ 4) When 16 subjects given 10 ml of aged garlic extract [derived from 6-7 garlic cloves] daily for
3 months, the peak plasma concentration of acetaminophen was significantly increased after 1
month, while after 2 months its bioavailability significantly increased and renal clearance
decreased (PO in human study). [Acetaminophen, or paracetamol, requires metabolic conversion
for its bioactivation.] The extract caused no significant effect after 3 months on CYP 2E1
metabolism of acetaminophen, but the bioavailability of its inactive glucuronide conjugate did
significantly increase. The extract used minced garlic incubated in 15-20% alcohol for 8-12
months and had as its major constituent S-allyl-L-cyseine, but very little diallyl sulfide. 1815
Garlic and its S-allyl components inhibit cytochrome P450 2E1 oxidation of acetaminophen
and thereby reduce its bioactivation (in vitro).540
IV. [1) May enhance cholesterol-lowering agents due to additive effects (speculative).777
900 mg daily of garlic tablets with 0.6% allicin in 30 diabetes type 2 patients for 24 weeks
resulted in significantly lower total cholesterol, LDL-cholesterol, and triglycerides compared to
30 controls (PO in human clinical study).3089]
Ia. + 3) Aged garlic extract at 960 mg/day containing 2.4 mg S-allylcysteine was given for 12 weeks
to 25 patients with hypertension treated with ACE inhibitors [24%], angiotensin II receptor
antagonists [48%], calcium channel blockers [44%], beta-blockers [40%], and/or diuretics
[60%] and compared to 25 treated placebo-control subjects in a randomized, double-blind trial
(PO in human clinical study). In patients with hypertension uncontrolled by drugs having a
systolic blood pressure > 140 mm Hg, the addition of the aged garlic extract lowered the blood
pressure significantly compared to controls.2757
39
+ 4) When 60 patients with tubercular lymphadenitis were treated with a 4-drug antituberculare
therapy of isoniazid, rifampicin, ethambutol, and pyrazinamide for 60 days, half were given 3-
6 pearls of garlic extract in divided doses on days 31-45 (PO in human clinical study). The garlic
relieved the dyspepsia in all the patients receiving it with the drugs, and significantly increased
the antitubercular activity of the serum, compared to the drugs alone. Liver function blood tests
remained normal in both groups.3169
An aqueous extract of garlic cloves has been shown to inhibit the growth of 2 strains of
multidrug-resistant Mycobacterium tuberculosis by 72% each (in vitro)3170 and to reduce the
individual minimum inhibitory concentration of the drugs isoniazid and rifampicin (in vitro).3171
Ib. + 1) A woman with chronic symptomatic group B streptococcus vaginitis resistant to antibiotics
obtained relief with a half clove of freshly cut garlic inserted each night for 1-4 weeks along with
local treatment with 0.5 g of 1% chorhexidine gel every 4-7 nights (vaginally). Of 8 other cases
lasting from 6 months to 5 years and unsuccessfully treated with one or more 10-14 day courses
of antibiotics such amoxicillin or azithromycin, and in most cases also with oral probiotics or
local tea tree oil (Melaleuca leucodendron), 7 then using only fresh cut garlic obtained
symptomatic relief while 1 found the local fresh garlic too irritating to use (vaginally).2711
IIa. 4) Raw garlic extracts protected from stomach damage by 100% ethanol (PO in rats).1263
The homogenized bulb or leaves at 250 mg/kg for 5 days, when followed by a single
hepatotoxic dose of alcohol, resulted in higher levels of glutathione and ascorbic acid and lower
malondialdehyde, while significantly enhancing catalase and glutathione reductase activities,
compared to those exposed to ethanol only (PO in rats).3166
5) Aged garlic extract helped protect animals from cardiotoxicity by doxorubicin (IP in
mice).1273
In addition, when garlic aqueous extract was given at 125 and 250 mg/kg after doxorubicin
damage to heart muscle, it significantly and dose-dependently reduced cardiotoxicity markers in
the heart tissue and serum, decreased changes induced in ECG parameters, and increased
antioxidant enzyme activity reduced by doxorubicin (PO in rats). The therapeutic effects were
enhanced for both doses when combined with 60 mg/kg atorvastatin.3313
6) Garlic leaves as 2% of diet1911 reduced kidney toxicity from gentamicin, preventing necrosis
and oxidative changes (PO in rats).1911,1912,1913
Likewise, powdered dry garlic bulbs fed as 4% of the diet for 27 days before 3 days of
gentamicin injections led to significantly reduced AST levels, a marker of liver inflammation, and
improved antioxidant status (PO in rats).3387
+ 7) The intake for 3 weeks of fresh garlic homogenate in 125 or 250 mg/kg doses or equivalent
amounts of S-allyl cysteine sulfoxide [SACS; 0.111 or 0.222 mg/kg], alone or together with the
ACE inhibitor captopril in the last week, for fructose-induced high blood pressure led
significant reductions in systolic blood pressure, heart rate, cholesterol, triglycerides, and glucose
compared to the fructose control group (PO in rats). The greatest reductions occurred with the
high garlic homogenate dose with captopril, suggesting greater biological activity than SACS
alone. SACS demonstrated synergistic effects with captopril for reducing blood pressure (PO in
rats) and in ACE inhibition (in vitro).2756
Before heart damage induced by isoproterenol, 250 mg/kg of garlic homogenate was given
for 30 days including the last 7 days with captopril (PO in rats). While the garlic and captopril
both significantly prevented superoxide dismutase and catalase reductions in heart tissue induced
by isoproterenol, the combination was even more effective in protecting the myocardium from
injury.3518
GINGER p. 166
Zingiber officinale rhizome
Contraindications
40
II. 2) Avoid large doses prior to surgery to avoid risk of hemorrhage (speculative),428 due to
inhibition of platelet aggregation (in vitro).292,294
In a placebo-controlled, crossover study with 30 healthy men, 50 grams of butter given with or
without 5 grams of powdered ginger in capsules led to an 18.8% decrease in fibrinolytic activity
with only the butter but a 6.7% fibrinolytic activity increase with the butter plus ginger (PO in
human study).3449
HOWEVER, a 2015 systematic literature review that included 8 clinical trials and 2
observational trials concluded that the evidence is equivocal on whether ginger affects
coagulation and platelet aggregation (PO in humans). The results appear dependent upon dosage
and subject characteristics such as being healthy or not.3543
Drug Interactions
II. + 2) The oral administration of cyclosporine in conjunction with, or 2 hours after, 5 ml/kg ginger
juice led to significantly reduced peak serum concentrations [by 71% and 51%, respectively] and
bioavailability [by 63% and 40%, respectively], compared with cyclosporine consumption alone
(PO in rats). There was no reduction in peak serum concentration or bioavailability when
cyclosporine was injected IV in combination with PO ginger juice, indicating the interaction most
likely occurred in the absorption phase. Ginger juice did not alter the efflux of rhodamine 123
from the serosal to the mucosal surface of jejunum or ileium section, demonstrating that it did not
increase the activity of P-glycoprotein as a means of reducing cyclosporine absorption.3472
Ia. 1) When 1.0 gm of powdered ginger was given prior to surgery to 20 women, it reduced nausea
from anesthetics thiopental, alcuronium, and/or vecuronium compared to 20 controls (PO in
The same 1 gram dose of powdered ginger given 1 hour before surgery with anesthesia in a
randomized, placebo-controlled, double-blind study with 160 patients resulted in a significantly
lower nausea score average and a borderline significant lower frequency of nausea 2 hours after
surgery, compared to those receiving placebo (PO in human clinical study). While nausea score
and frequency were also lower with ginger than placebo after 4 and 6 hours post operation, the
differences were not significant.3417
3) Ginger before and after chemotherapy controlled nausea and vomiting from
cyclophosphamide (PO in human clinical study).1598
When 500 mg dried and powdered ginger 3 times daily for 4 days was given to advanced
breast cancer patients with nausea from standard chemotherapy of docetaxel, epirubicin, and
cyclophosphamide while being treated with the standard antiemetic regimen of granisetron plus
dexamethasone, those 37 who received ginger had significantly reduced nausea from 6-24 hours
postchemotherapy compared to the 41 patients using only standard antiemetics, but not beyond
the first day (PO in human clinical study).3092 In a randomized, placebo-controlled, single-blind,
crossover study, 60 breast cancer patients were using either high emetic risk chemotherapy, 75%
5-flouracil, epirubicin, and cyclophosphamide and 11.7% docetaxel, doxorubicin, and
cyclophosphamide, or were given low emetic risk docetaxel alone (IH in human clinical study).
Ginger essential oil aromatherapy on a necklace was used for 5 days, and the same was done with
artificial ginger fragrance placebo. The ginger essential oil led to a significant reduction in the
score for acute nausea, but it was not sustained. The essential oil also significantly improved
global health status, role functioning, and appetite loss.3537
4) In a randomized crossover study with 48 gynecologic cancer patients receiving cisplatin
therapy along with the antiemetic drug metoclopramide 8 times the first day, 1 gram daily of
ginger for the first 5 days after chemotherapy was as effective in controlling nausea and
vomiting as was continuing for 5 days the standard drug metoclopramide which was more
associated with restlessness (PO in human clinical study).2534
In high emetogenic chemotherapy cycles with cisplatin and doxorubicin for bone sarcoma in
25 children and 35 young adults, when ginger capsules or placebos were added to treatment with
41
the antiemetic drugs ondansetron and dexamethasone to help control the drug-induced nausea
and vomiting, compared to placebo the ginger significantly reduced acute moderate to severe
nausea [93% vs. 56%, respectively] and vomiting [77% vs. 33%, respectively] (PO in human
clinical study). Likewise, compared to placebo the ginger decreased significantly the delayed
moderate to severe nausea [73% vs. 26%, respectively] and vomiting [47% vs. 15%,
respectively]. For patients weighing 20-40 kg, 3 doses of 334 mg of ginger were used, while
those from 40-60 kg received 2 doses of 800 mg each at 1 hour before and 3 after and a 400 mg
dose 8 hours after chemotherapy infusions.2909
+ 7) In a randomized, placebo-controlled, double-blind trial with 41 patients with diabetes type 2
treated with oral hypoglycemics, 22 received 2 grams daily of ginger powder for 12 weeks (PO
in human clinical trial). After 12 weeks the ginger group had significantly reduced fasting blood
sugar, glycosylated hemoglobin, apolipoprotein B and malondialdehyde compared to baseline and
to the placebo group. Those using ginger also had a significantly increased level of apolipoprotein
A.3501
IIa. 1) Ginger extract significantly reduced mucosal stomach damage by 70% ethanol (alcohol) by
inhibiting reduction of mucin content (PO in rats).498
Ginger as 0.05% of the diet for 8 weeks followed by an acute exposure to ethanol showed
gastroprotective effects by significantly increasing activity of the endogenous antioxidant
enzymes superoxide dismutase, glutathione reductase, and glutathion-S-transferase in the
stomach and intestinal mucosa and increasing mucin content in stomach mucosa, compared to
having no exposure to the spice (PO in rats).3347
+ 3) A 50% ethanol extract given at daily doses of 400 mg/kg with 20 or 80 mg/kg of atorvastatin
for 4 weeks significantly decreased high cholesterol more than the atorvastatin doses given alone
or the control (PO in rats). Ginger extracts significant diminished the reductions by atorvastatin of
liver superoxide dismutate and catalase levels. In addition, the combinations of ginger extract
with the 2 atorvastatin doses significantly reduced the atorvastatin-induced serum
aminotransferase elevations and increases in liver malondialdehyde and nitric oxide, so that the
lower atorvastatin combination dosage no longer caused significant elevations of these levels.2849
+ 4) An ethanolic ginger extract, when given at 200 to 600 mg/kg together with 2.5 mg/kg
morphine, significantly and dose-dependently enhanced the morphine analgesia in reducing the
response to pain induced by radiant heat, compared to morphine alone (IP in rats).3321
addition of 0.05g% of ginger to the diet, compared to the same diet without ginger (PO in rats).
Calcium absorption was improved the most. Ginger increased the uptake of iron better than either
piperine or capsaicin.3471
+ 6) When given concurrently with a 600 mg/kg IP dose of acetaminophen that by itself induces
hepatotoxicity, 100 mg/kg of powdered ginger as an aqueous suspension significantly reduced
liver toxicity markers alanine aminotransferase [ALT], aspartate aminotransferase [AST], and
alkaline phosphatase [ALP], along with lowering plasma bilirubin (PO in rats). The marker of
oxidative stress malondialdehyde [MDA] was also reduced, while hepatic necrosis and cellular
vacuolization were substantially decreased. The effects of ginger were comparable to vitamin
E.3475 A hydro-alcoholic extract of ginger at 200 mg/kg given 1 hour before a single 3 g/kg oral
dose of acetaminophen significantly reduced the activies of serum transaminases and ALP,
compared to the acetaminophen dose alone that induced hepatotoxicity (PO in rats). MDA was
likewise significantly reduced, while superoxid dismutase and glutathione-S-transferase was
significantly increased with the extract before the drug, compared to acetominophen without it.
Centrilobular necrosis from acetaminophen toxicity was greatly diminished with extract use.3473
In a study in which 0.1 ml/kg ginger oil extracted with alcohol was given 2, 6, and 10 hours after
a 600 mg/kg hepatotoxic dose of acetaminophen PO, serum AST, ALT, ALP, and sorbitol and
glutamate dehydrogenases were all significantly reduced (PO in rats).3474
42
GINKGO p. 170
Ginkgo biloba leaves
Contraindications
I. 2) Avoid or use caution in bleeding disorders428,1890,2960 due to potential association with
hemorrhage (PO in human case reports).195,525,1190,1191,1449
In a retrospective population study of about 200,000 ambulatory patients in the Taiwan
Longitudinal Health Insurance Database, 7700 using ginkgo extract showed significantly higher
risks of hemorrhage among males and those ≥ 65 years of age (PO in human study).2960
HOWEVER, In a randomized, placebo-controlled, double-blind crossover study with 50
healthy male subjects, 120 mg of EGb 761 twice daily for 1 week did not show any evidence of
inhibition of platelet aggregation or blood coagulation, based on 29 parameters assessed (PO in
human study).3445
II. 1) Do not use before elective surgery (speculative)428,703,1309,1310,1782,1890 since ginkgo may
contribute to hemorrhage.
In a retrospective population study of about 200,000 ambulatory patients in the Taiwan
Longitudinal Health Insurance Database, 7700 using ginkgo extract showed significantly higher
risks of hemorrhage among males and those ≥ 65 years of age (PO in human study).2960
Drug Interactions
Ia. 1) When ginkgo extract was taken for 28 days, it reduced the bioavailability of CYP 2C9
substrate tolbutamide and its effect on lowering blood glucose (PO in human study).2015
To animals fed a low protein diet of 7% casein for 3 weeks, along with controls with a normal
protein diet with 20% casein, ginkgo extract was given at 100 mg/kg daily for 5 days, combined
with the hypoglycemic drug tolbutamide on the last day (PO in rats). In the control rats the
ginkgo had little influence on the tolbutamide hypoglycemic effect though the plasma drug
concentration tended to be low, but in the low-protein rats the plasma concentration and
hypoglycemic effect were both significantly reduced. Ginkgo extract markedly increased CYP 2C
activity in both groups, but significantly moreso in rats with low protein intake.3529
3) 120 mg/day of ginkgo for 18 days increased plasma nifedipine 53% (PO in human study).1728
When 240 mg of standardized extract was given only once to 8 healthy young men
simultaneously with nifedipine and compared to nifedipine alone in an open, random crossover
trial, there was no significant change in the maximal plasma concentration of nifedipine, though
its average value did increase by about 30% with the combination (PO in human study). For 2 of
the subjects, the values were about twice as great, and they had more severe and longer headaches
with the extract than without it. Also, the average heart rate of the group tended to be additionally
faster by 2-9% with the combination than the 5-11% increase with nifedipine alone. So, it was
recommended to avoid the combination when possible and to monitor carefully when ginkgo and
nifedipine are taken together.3229
HOWEVER, in a study of 20 patients each taking the hormonal CYP 3A4 substrates
anastrozole, letrozole, or tamoxifen, there were no significant changes in trough concentration
after taking 240 mg daily of EGb 761 for 3 weeks.3268 Based on clinical relevance, the
pharmacokinetic interaction risk has been assessed as low in doses of the standardized extract of
≤ 240 mg/day (speculative).3222
4) A dose of 360 mg/day of EGb 761 increased bioavailability of CYP 3A4 substrate midazolam
by 25% and decreased its oral clearance by 26% (PO in humans study).2015
HOWEVER, in another study with 14 healthy subjects, 240 mg daily for 4 weeks significantly
reduced midazolam bioavailability by 34% and its maximum concentration by 31%, but half-life
was not changed, indicative of intestinal, but not hepatic, induction. Still, the same dose for 2
weeks had no effect on the combination of lopinavir and ritonavir, probably due to ritonavir's
CYP3A4 inhibiting activity.3135 Based on clinical relevance, the pharmacokinetic interaction risk
has been assessed as low in doses of the standardized extract of ≤ 240 mg/day (speculative).3222
43
5) Taking 360 mg extract daily for 14 days significantly increased talinolol bioavailability due
to inhibition of P-glycoprotein efflux (PO in human study).2680,3138 The bioavailability and peak
plasma concentration of talinolol were significantly increased in 12 healthy subjects by ginkgo
extract by 21% and 33%, respectively, while its half-life increased of 11% was not significant
(PO in human study).3138 Based on clinical relevance, the pharmacokinetic interaction risk has
been assessed as low in doses of the standardized extract of ≤ 240 mg/day (speculative).3222
Ib. 1) 80 mg extract daily was associated with spontaneous bleeding, following 3-year use of aspirin
as an antiplatelet drug (PO in human case report).194
HOWEVER, a [CORRECTION insert: half-maximal inhibition of] PAF-induced aggregation
of human platelets experimentally requires a concentration of 100 times or more greater than is
achieved in the plasma by normal therapeutic doses of 120-240 mg of a 50:1 concentrated ginkgo
extract (in vitro).1747
5) Warfarin use in a 78-year-old woman resulted in intracerebral hemorrhage after the addition
of ginkgo for 2 months (human case report).524
HOWEVER, in a retrospective population study of about 200,000 ambulatory patients in the
Taiwan Longitudinal Health Insurance Database, 7700 using ginkgo extract showed there was not
a higher hemorrhage risk associated with the 60 concurrently taking warfarin or antiplatelet drugs
[colpidogrel, cilostazol, ticlopidine], though there were significantly higher risks of hemorrhage
among males and those ≥ 65 years of age (PO in human study). 2960
+ 7) The introduction of ginkgo extract at 160 mg/day for 2 weeks after 3 years of uneventful use
of risperidone resulted in priapism that required emergency hospital treatment (PO in human
case report). The ginkgo and risperidone were discontinued, and when the risperidone alone was
reintroduced, no further episodes of priapism occurred during the 6 months of follow-up.3230
+ 8) A man who was very drug-compliant had been taking efavirenz for 2 years in combination
with 2 other drugs. A virological failure developed that involved a mutation in the reverse
transcriptase gene. Plasma efavirenz levels in blood samples dating back 15 months were shown
to steadily decrease over time. The only change in comedication during this time was his taking a
ginkgo product for "some months". This was thought to be the probable cause, possibly due to
induction of CYP3A4.3392
II. + 5) When ginkgo leaves were decocted and the extract given together with oral cyclosporine, the
maximum concentration of cyclosporin was reduced by 62%, and its bioavailability decreased by
51%, though no effects was shown when cyclosporin was given IV (PO in rats). When given
onion (Allium cepa) juice instead, another rich source of quercetin containing 2.5 times that of the
ginkgo extract, the combination with oral cyclosporin reduced the peak concentration by 60% and
the bioavailability of cyclosporin by 68%, but again no effect on IV cyclosporin. This indicates
that the interaction occurred by reducing absorption. No effect was shown by onion juice on Pgp,
whereas ginkgo paradoxically inhibits Pgp (in vitro) that would result in an increase in
cyclosporine absorption.3192
Ia. 2) A study of osteoarthritis used extracts from ginger and galangal; acetaminophen was
allowed for pain (PO in human clinical study). Reduced pain on standing after using the extract
was significantly better than for placebo, and stiffness and pain after walking were also improved
by the extracts.1409
A 1-month randomized, placebo-controlled, double-blind study using 30 mg/day of a 33.3:1
ginger ethanolic extract or 400 mg ibuprofen 3 time daily or placebo in groups of 40 each of
osteoarthritis patients with moderate to severe pain showed that scores for pain and regressive
pain after rising were significantly greater for placebo than for the extract or ibuprofen (PO in
human clinical study). Acetaminophen was allowed in both groups, and there was no significant
difference in pain scores between ginger extract and ibuprofen.3314 Twenty knee osteoarthritis
patients received a capsule with 250 mg supercritical carbon dioxide extract of ginger 4 time
daily or placebo for 12 weeks in a 6-month randomized, placebo-controlled, double-blind,
44
crossover trial and used handicap and the visual analog scale for pain on movement and as
outcome measures (PO in human clinical study). Acetaminophen was allowed in both groups, and
at the end of the study, the ginger extract group had highly significant decreased handicap and
pain on movement compared to placebo.3316
A randomized, double-blind, controlled study of 43 osteoarthritis patients with former
gastropathy or dyspepsia from NSAIDs compared giving 200 mg/day of a 20:1 ginger extract in
170 mg lipid combined with 500 mg glucosamine to 21 patients to giving 100 mg diclofenac to
22 patients for 4 weeks (PO in human clinical study). Afterward, the diclofenac group had
increased severity of dyspepsia pain, stomach mucosa degeneration, and a decrease in stomach
prostaglandins (PG), while ginger group had no change in stomach pain and increased levels of
PGE1, PGE2, and PGF indicative of mucosal protection. Both groups had significantly lower
osteoarthritis pain on standing and moving.3315
5) Ginkgo leaf extract given to schizophrenia patients together with haloperidol increased the
effectiveness and reduced the extrapyramidal side effects of the medication (PO in human clinical
study).1281
A review and meta-analysis of 6 randomized studies lasting at least 8 weeks and using
standardized ginkgo extract as an add-on therapy for chronic schizophrenia in 466 cases
compared to 362 patients on placebo [except in 1 study] found significant improvement in
negative symptoms with chlorpromazine and clozapine and in total symptoms with
chlorpromazine (PO in human clinical studies).2760 In addition, of 157 schizophrenic patients with
tardive dyskinesia taking chlorpromazine, those 78 also taking EGb 761 for 12 weeks had a
significant decrease in Abnormal Involuntary Movement Scale [AIMS] score, compared to 79
taking placebo, but there was no difference in positive or negative symptoms (PO in human
clinical study).3292 In 15 chronic schizophrenic patients given 300 mg/day EGb 761 for 8 weeks
together with olanzapine, compared with 14 taking olanzapine only, significant improvements in
positive symptoms and decreases in superoxide dismutase and catalase levels were found with the
ginkgo group (PO in human clinical study).3291
+ 7) In two randomized, placebo-controlled, double-blind studies in which radioiodine [I-131] was
used to treat 25 patients with Graves' disease 3095 and 23 thyroid cancer patients postsurgically
for thyroid remnant ablation,3096 those who received 120 mg EGb 761 daily for 3 days before and
a month after the I-131 had less chromosome damage as shown by significantly fewer
micronucleated lymphocytes and clastogenic factors than those who received placebo (PO in
human clinical study).3095,3096
+ 8) In 828 mild to moderate Alzheimer's disease patients receiving conventional therapy with the
cholinesterase inhibitors donepezil, galantamine, or rivastigmine, 29 also were taking ginkgo
extract EGb 761, most at a dose of 120 mg daily (PO in human clinical study). After a 1-year
follow-up, the score on the Mini Mental State Examination [MMSE] was significantly improved
for those using the ginkgo extract compared to conventional therapy alone. The MMSE effect
seen after 6 months was positive, but not significant.3484
+ 9) In a 2-month, randomized, placebo-controlled, double-blind trial involving 111 patients with
acne, a topical gel with 0.1% adapalene was used as the primary treatment after evening facial
cleansing, while 55 also used a cream containing ginkgo extract, bakuchiol, and mannitol after
morning facial cleansing (TP in human clinical study). Those using the adapalene gel with ginkgo
cream had significantly improved inflammatory lesions, IgA, and seborrhea intesity, compared to
those using the adapalen gel and placebo cream. Subject perception and global efficacy
assessments also indicated superiority of the ginkgo cream. Safety and local tolerance of the
ginkgo cream were good.3499
IIa. + 2) After osteoporosis was induced by administering dexamethasone for 5 weeks, ginkgo
standardized extract at 14 mg/kg or more daily significantly increased the percentage of alveolar
bone of the mandible and at 28 mg/kg or more daily significantly increased the percentage of
trabecular bone in the femur, compared to controls (PO in rats).3147
45
+ 3) Doses of a standardized extract prepared with phospholipids at 3:1 [phytosome] and given at
100 mg/kg for 30 days helped protect against heart damage induced in the last 2 days by 2 doses
of subcutaneous isoproterenol at 85 mg/kg (PO in rats). The extract significantly increased
cardiac levels of glutathione and the antioxidant enzymes superoxide dismutase, catalase,
glutathione peroxidase, and glutathione reductase, as well as reducing the lipid peroxidation
marker malondialdehyde in the heart and cardiac damage markers AST, LDH, and CPK in the
serum.3185
+ 4) The ototoxicity caused by excessive gentamicin including auditory brain stem response
threshold, cochlear hair cell damage ratio, and apoptosis was prevented with 100 mg/kg of EGb
761 for 2 days prior plus concurrently (PO in guinea pigs). The protection was believed to be due
to a reduced formation of reactive oxygen species and nitric oxide-related mechanism as shown in
cultured cochlear cells (in vitro).3260
+ 5) When 30 mice received 2 mg/kg cisplatin twice weekly for 9 doses, half were also given
about 100 mg/kg EGb761 daily in the drinking water, and comparisons were made for cisplatin-
induced peripheral neuropathy (PO in mice). A control and ginkgo-only group were also
monitored. The cisplatin plus ginkgo group had significantly less reduction in nerve conduction
velocity and dorsal root ganglia growth retardation than the cisplatin-only group. The ginkgo-
only group was similar to controls in these outcomes.3373
GOLDENSEAL p. 182
*Hydrastis canadensis roots/rhizome
Contraindications
II. 1) Do not use in jaundice in newborns (speculative).777,1890
Drug Interactions
Ia. 1) A dose of 2.7 gram goldenseal extract daily for 28 days inhibited metabolism of CYP3A4
substrate midazolam by 40% in 12 healthy subjects (PO in human study).1807 Berberine at 300
mg 3 times daily for 14 days in 17 healthy males significantly increased the bioavailablity of CYP
3A4 substrate midazolam by 40% and its maximum plasma concentration by 38%, and
significantly decreased its oral clearance by 27% (PO in human study).3238 Also, 3.97 gram of the
root extract delivering 132 mg hydrastine and 77 mg berberine per day for 14 days significantly
[Note CORRECTION: not "reduced"] INCREASED midazolam bioavailability in 16 healthy
subjects (PO in human study).2501
Based on clinical relevance, the pharmacokinetic interaction risk with drugs that are substrates
of CYP 3A4 or 2D6 has been assessed as high (speculative).3222
3) The combination of 1500 mg berberine daily for 3 months in 43 type 2 diabetes patients with
46
urinary ratio of the CYP 2C9 substrate losartan to its metabolite E-3174 (PO in human study).3238
study).2907
(speculative).2753
for disseminated candidiasis to 36 days from 17 days and 14 days, respectively, when these 2
antifungal agents were used separately, and compared to 12 days for controls (IP in mice).3107
47
by doxorubicin.3148
IIb. 1) Berberine reduced bacterial resistance to penicillin and chloromycetin of enteric bacteria
previously been unaffected by these antibiotics (in vitro).578
A 1:5 extract [g of goldenseal leaf to ml of 50% ethanolic solvent] with a minimum inhibitory
concentration [MIC] of 75 mcg/ml was twice as active against methicillin-resistant
Staphylococcus aureus [MRSA] as isolated berberine with an MIC of 150 mcg/ml (in vitro).3130
GRAPEFRUIT p. 186
Citrus paradisi fruit / juice
Drug Interactions
Ia. 16) [CORRECTION: The interaction and its reference citation #2590 in the text was listed
previously as number 8) with citation #1274. Therefore, the following interaction and citation are
new.]
+ When grapefruit juice or water was given with the CYP 3A4 substrate erythromycin to 6 healthy
men, the grapefruit juice significantly increased the maximum plasma concentration and
bioavailability of the antibiotic erythromycin, compared to water (PO in human study).2590
+ 21) When 17 patients with Addison's disease receiving cortisol were given 200 ml of pink
grapefruit juice 3 times daily for 3 days, the juice significantly increased median serum cortisol
levels over a 2.6 hour period, with a 19% increased cortisol bioavailability over that time (PO in
human clinical study). The median urinary allo- plus tetrahydrocortisol/tetrahydrocortisone ratio
was also significantly increased.3021
+ 22) The chemotherapeutic drug sirolimus showed 350% greater bioavailability when taken once
weekly in conjunction with 240 ml of grapefruit juice once daily in a phase I pharmacokinetic
study with 101 advanced cancer patients taking either this combination, sirolimus alone, or
sirolimus with ketoconazole (PO in human clinical study). The authors note that lower doses of
sirolimus are possible with simultaneous consumption of a consistent source of grapefruit juice to
provide equivalent blood levels of the drug.3144
Ib. + 4) Following a liver transplant, a 52-year-old man stabilized on tacrolimus as part of his
medication began after 4 months to experience toxicity symptoms and highly elevated blood
levels of the drug (PO in human case report). He had been warned to avoid grapefruit
consumption, but a friend had given him orange marmalade he craved that was home-made with
half grapefruit to supply the bitter flavor, and he consumed over 3 lbs of it in the week prior to the
toxic symptoms.3124
GUARANA p. 194
Paullinia cupana seeds
Drug Interactions
II. 1) When 821 mg/kg of guarana extract was taken simultaneously with a single dose 50 mg/kg
oral amiodarone, there were significant reductions in peak plasma levels, tissue levels, and
bioavailability of the drug (PO in rats). However, when the same dose of guarana extract was
taken for 14 days prior to administration of a single dose of amiodarone, there was no significant
effect on its pharmacokinetics. Apparently, the guarana extract interacts with amiodarone in the
gastrointestinal tract.3423
Ia. + 1) The cancer-related fatigue in 60 breast cancer patients receiving systemic chemotherapy,
including 81% or more receiving a combination of doxorubicin and cyclophosphamide with or
without fluorouracil, was treated using guarana extract at 50 mg twice daily, providing 6.5 mg of
48
caffeine for 21 days in a randomized, placebo-controlled, crossover design trial (PO in human
clinical trial). Several questionaire tools documented significant improvements in global fatigue
scores when the extract was used immediately after chemotherapy , when compared to placebo
use, while neither anxiety or depression nor insomnia were worsened.2920
HOWEVER, a 75 mg daily dose of guarana was not found effective in relieving fatigue in a
randomized, blinded, crossover trial with 36 breast cancer patients undergoing radiation therapy
28 times over 35 days (PO in human clinical study).2921
GUGGUL p. 198
Commiphora mukul roots
Drug Interactions
Ib. 1) A man with a prosthetic heart valve given 3 mg/day warfarin to obtain an International
Normalized Ratio [INR] of 2.4 treated himself for bronchitis with an aqueous extract of guggul
roots 3 times daily (PO in human case report). A few days later his INR was reduced to 0.9. He
was hospitalized and given IV heparin, while stopping guggul use. After 3 days his INR returned
to normal.3523
HAWTHORN p. 199
Crataegus spp. leaves, flowers and/or fruit
Ia. 1) When compared to NYHA class II chronic heart failure patients on synthetic drugs only,
those class II patients using only C. oxyacantha leaf and flower extract or the extract in addition
to cardiac glycosides such as digoxin had significantly less fatigue, stress dyspnea, and
palpitations and required significantly fewer cardiac glycosides (PO in human clinical study).2238
HOWEVER, a study on digoxin immunoassays with 2 hawthorn hydroalcoholic extracts with
12% ethanol, one from the leaf, flower and berry and the other from the berry only, showed no
interference with the Tina-Quant assay, but the Digoxin III assay indicated falsely elevated levels
of digoxin for both both extracts, both alone and in the presence of digoxin (in vitro). Also, rat
heart muscle cells had increased intracellular calcium levels with both extracts but showed no
additive response with digoxin (in vitro). On the basis of these findings, the authors recommend
that patients on digitalis should avoid digoxin (speculative).3528
IIa. + 2) Dose-dependent gastroprotective activity againt stomach ulcers induced by ethanol was
comparable to that of ranitidine as shown with hawthorn berry ethanol extract given in a range of
50-200 mg/kg (PO in rats).
+ 3) The testicular toxicity caused by cyclophosphamide was partially ameliorated by a water
extract of C. monogyna berries given 4 hours after the drug at a dose of 20 mg/kg daily for 28
days (PO in rats). The weights of the testes and epididymides had lower weights and
spermatogenic activities were not as severe as with exposure to cyclophosamide only.3344
HIBISCUS NEW
^ (Hibiscus sabdariffa) flowers [for Hibiscus rosa-sinensis, now see Chinese hibiscus]
Drug Interactions
Ia. 1) When 1 L of a sweetened aqueous extract made with 30 g/L dried flowers was consumed 1.3
hours before acetaminophen (paracetamol) was taken by 6 healthy male subjects, the urinary
clearace was increased by 11.7%, thereby significantly reducing its terminal elimination half-life
by 47%, compared to consumption of water beforehand (PO in human study). The study authors
recommend that hibiscus extract be consumed 3-4 hours before acetaminophen to avoid
shortening it therapeutic effects (speculative).3511
2) A hibiscus beverage was taken with 600 mg tablets of the malarial drug chloroquine by 6
healthy men on an empty stomach after an overnight fast to assess its affect on the drug
absorption in comparison with water and lemonade (PO in human study). The bioavailability and
49
maximum plasma concentration were both significantly reduced by the hibiscus beverage and the
lemonade. This was believed to be due to their acidity (speculative).3512
3) A water infusion made from 30 g of dried flower per liter of boiled water was given in doses
of 300 ml daily for 3 days to 12 healthy subjects, and on the third day the beverage was taken
with 25 mg of diclofenac (PO in human study). In this randomized crossover study, compared to
taking diclofenac with water, the hibiscus infusion led to a significant reduction in excretion of
the drug during the 8 hours after its administration.3513
HOPS p. 203
Humulus lupulus strobiles
1a. + 1) A combination of 3 herbal hydroethanolic extracts including hops strobiles 4-8:1, valerian
(Valerian officinalis) root 3-6:1, and passion flower (Passiflora incarnata) herb 4-7:1 was found
to markedly improve symptoms associated with benzodiazepine withdrawal phase in 107
patients of an average age of 54 years (PO in human clinical study). The extracts were begun with
1-2 tablets daily as benzodiazepine dosage was reduced for 2 weeks, and continued for the next 4
weeks after benzodiazepine use was stopped. Improvement was shown for pronounced tiredness
in 76% and general unrest in 71%, according to subjective assessment of patients. Sleep improved
in 68% by the end of the treatment, and 74% had more motivation and drive than at the
beginning. At the end, 62% were calmer and better able to cope. No adverse drug events occurred
in any patients.2634
HORSE CHESTNUT p. 204

*Aesculus hippocastanum seeds
IIa. + 1) While suboptimal doses of the triterpenoid saponin mixture escin and corticosterone
individually had no effect on carrageenan-induced paw edema or pleural inflammation, the
combination of these agents at the same doses reduced the paw edema and the volume of pleural
exudates and the exudate white blood cells (PO in rats). Likewise, alone these agent had no
effects on inflammatory factors in macrophages stimulated by lipopolysaccharides, but together
they inhibited secretion of nitric oxide, TNF-, and interleukin 1 (in vitro).2837
JUJUBE p. 211
Ziziphus spinosa seeds
Drug Interactions
II. 1) Three fractions of the hexane extract were shown to potentiate sleeping time anesthesia from
hexobarbital and produce sedative effects (in mice).1254
As part of an alcoholic extract combination with 7.5 parts jujube, 2 parts each of the
nonsedative Szechuan lovage (Ligusticum chuanxiong) and the fungus fu-lin (Poria cocos), and 1
part each of the nonsedatives anemarrhena (Anemarrhena asphodeloides) and Chinese licorice
(Glycyrrhiza uralensis), 60 subjects with sleep disorders given 1 gram of this combination extract
suanzaorentang nightly for 2 weeks had significant improvements in sleep and well-being
compared to 1-week placebo period before active treatment (PO in human clinical study). Sleep
latency, sleep time number of awakenings, sleep quality and subjective feeling on arising were all
significantly enhanced. No side effects were noted.1219
KAVA p. 212
*Piper methysticum rhizomes and root
Contraindications
I. 1) Avoid operating a motor vehicle following excessive use of kava.244,728
50
HOWEVER, using a driving simulator, an acute therapeutic dose of kava water-soluble
extract with 180 mg kavalactones showed no impairment on driving outcomes when compared to
placebo in a crossover trial with 22 adults (PO in human study). On the other hand, the
benzodiazepine drug oxazepam significantly reduced braking reaction time and increased lapses
in concentration when compared to kava. Significantly decreased alertness over time was found
with oxazepam but not with kava or placebo.3251
II. 4) Consumption of kava products should be avoided in individuals with jaundice or past liver
disorders (speculative). 1232
Mold hepatotoxin contamination has also been raised as a possible explanation of the rare
cases of liver damage associated with kava (speculative).2913,3067 Cytotoxicity to liver cells of
isolated kavalactones was shown to be mild for kavain and moderate for methysticin at
supraphysiological concentrations of 200 mcM each, whereas yangonin was markedly cytotoxic
at 25 mcM due primarily to apoptosis but not to glutathione depletion (in vitro).2844 Yangonin had
previously been shown to have an IC50 of 14-16 mcM, greater than desmethoxyyangonin at 53-59
mcM, levels over 100 mcM for methysticin, and 49-53 mcg/mL for kava ethanolic extract (in
vitro).1643
HOWEVER, another hepatotoxic agent in kava root, the chalcone flavokawain B [FKB] has
been identified as the active hepatotoxin (in vitro) and in vivo at 25 mg/kg (PO in mice). FKB is
preferentially extracted in lipophilic solvents 160-fold over water; in the dried extracts, FKB was
at 0.2 mg/g for water, 32.3 mg/g for 95% ethanol, and 33.7 mg/g for acetone. FKB is a potent
hepatotoxin sensitive to reduced glutathione, and its levels in kava-containing preparations should
be specifically monitored and controlled.2709 The combination of using organic solvents including
acetone and ethanol to extract "2-day" [rather than "noble"] cultivars of kava higher in the
lipophilic FKB, dihydromethysticin, yangonin, and desmethoxyyangonin is a probable
explanation for many of the cases of liver toxicity possibly or probably due to kava extract
consumption (speculative).3507
Drug Interactions
Ia. 1) Intoxication increased when kava was taken with alcohol compared to alcohol alone (PO in
human study).1025
Alcohol is often consumed concurrently with kava in kava-associated hepatotoxicity cases (PO in
case series), and there may be a metabolic interaction with ethanol that could facilitate liver
damage (speculative).2710 Based on clinical relevance, the pharmacokinetic interaction risk has
been assessed as low (speculative).3222
III. 1) Kavalactone-concentrated products equivalent to those associated with adverse effects on the
liver should be avoided in individuals taking any liver-toxic drugs (speculative); cases of liver
toxicity associated with acetone and ethanolic standardized extracts have been reported in
Germany and Switzerland.1232
HOWEVER, the chalcone flavokawain B [FKB] has been identified as the active hepatotoxin
(in vitro) and in vivo at 25 mg/kg (PO in mice). FKB is preferentially extracted in lipophilic
solvents 160-fold over water; in the dried extracts, FKB was at 0.2 mg/g for water, 32.3 mg/g for
95% ethanol, and 33.7 mg/g for acetone. FKB is a potent hepatotoxin sensitive to reduced
glutathione, and its levels in kava-containing preparations should be specifically monitored and
controlled.2709 The combination of using organic solvents including acetone and ethanol to extract
"2-day" [rather than "noble"] cultivars of kava higher in the lipophilic FKB, dihydromethysticin,
yangonin, and desmethoxyyangonin is a probable explanation for many of the cases of liver
toxicity possibly or probably due to kava extract consumption (speculative).3507 Cytotoxicity to
liver cells of isolated kavalactones was shown to be mild for kavain and moderate for methysticin
at supraphysiological concentrations of 200 mcM each, whereas yangonin was markedly
cytotoxic at 25 mcM due primarily to apoptosis but not to glutathione depletion (in vitro).2844
Yangonin had previously been shown to have an IC50 of 14-16 mcM, greater than
51
desmethoxyyangonin at 53-59 mcM, levels over 100 mcM for methysticin, and 49-53 mcg/mL
for kava ethanolic extract (in vitro).1643
KUDZU p. 221
Pueraria lobata = Pueraria montana var. lobata = Pueraria thunbergiana root
I. 1) When kudzu root was used by alcohol abusers, about 80% no longer experienced alcohol
craving after 2-4 weeks (empirical).546
When 1200 mg daily was given to 10 healthy adults prior to drinking sessions in a double-
blind, placebo-controlled crossover trial, beer consumption was significantly reduced from 3.5 to
2.4 beers per session, and those on puerarin took smaller sips, drank more slowly, and waited
longer between beers (PO in human study).3221
In addition, in a randomized, placebo-controlled, double-blind study of 17 young men
consuming about 28 alcoholic drinks weekly and not seeking treatment but diagnosed with
alcohol abuse or dependence, a 2-week run-in for baseline values was followed by 4 weeks of
treatment with 250 mg of kudzu isoflavones 3 times daily for 10 men and placebo for 7 men, and
then 2 weeks of follow-up (PO in human clinical study). There were no adverse events or changes
in blood chemistry, and adherence was excellent. The men taking the kudzu isoflavones in
comparison to placebo significantly reduced the number of drinks per week by 34-57%, the
percent of days abstinent, and the consecutive number of days abstinent, and also decreased the
number of days of heavy drinking. In the follow-up stage, the reductions in the kudzu group
remained significantly less than baseline values.3509
Puerarin at 30-120 mg/kg significantly and dose-dependently increased serum levels of
alcohol dehydrogenase (ADH) and ALDH and subsequently decreased liver levels of CYPs 1A2,
2E1, and 3A induced by ethanol intake (PO in rats). It also reduced hepatocellular lesions.3283
IIb. + 1) The ethanolic extract of the root at concentrations from 5-100 mcg/ml prevented auditory
hair cell damage caused by the chemotherapy drug cisplatin (in vitro). This effect was due to
inhibition of lipid peroxidation and enhanced scavenging of free radicals (in vitro).2724
KUTAKI p. 222
Picrorhiza kurroa rhizome/roots
IIa. + 4) The iridoid glycoside fraction of the ethanolic fraction of kutaki at 12 mg/kg daily for 15 days
with ethanol reduced the hepatotoxicity from the concurrent and prior 30 days of alcohol
consumption, compared to the alcohol consumption alone (PO in rats). The extract group had
significant increases in liver acetaldehyde dehydrogenase for alcohol metabolism, as well as the
antioxidant enzymes superoxide dismutase, catalase, peroxidase, and glutathione-S-transferase.
The extract-fed rats also had significantly lower hepatic GGT, acid phosphatase, lipid peroxides,
and bilirubin, among other indicators. Significant reductions in serum enzyme activities for the
extract group included ADH, GGT, AlkPhos, GOT, and GPT and serum chemical markers
bilirubin and triglycerides.2936
+ 5) The iridoid glycoside fraction of the ethanolic fraction of kutaki, given at 1 mg/kg for 14 days
prior to experimental malaria infection with multidrug-resistant Plasmodium yoelii subsequently
treated for 3 days with suboptimal intraperitoneal dose of chloroquine, resulted in effective
treatment based on survival and parasitic load, compared to treatment failure using chloroquine
without the extract pretreatment (PO in mice). Extract use for 14 days was shown to enhance
immune response by significantly increasing ovalbumin antigen-induced T-cell proliferation and
activation and antigen-specific antibody production, compared to controls.2937
+ 6) The combination of 2 iridoid glycosides, 1 part picroside-I and 1.5 parts kutkoside, given for 7
days at 6 mg/kg blocked the hepatotoxicity of acetaminophen (paracetamol) given after day 7
52
ethinylestradiol given on days 5-7 as indicated by its anticholestatic effect (PO in rats and guinea
pigs).3160 The same results were shown with the 12 mg/kg of the combination when given
concurrently for 6 days with the hepatotoxin rifampicin (PO in rats and guinea pigs).3161 The
changes in bile volume and the content of bile salts and bile acids caused by the 3 drugs in
untreated animals were antagonized by both doses of the iridoid glycosides, and the effects were
greater in all of these parameters than those achieved with 20 mg/kg of silymarin.3160,3161 The
reduced viability of hepatocytes and reduction in oxygen uptake rate induced by rifampicin was
also reversed more effectively by the 12 mg/kg of the glycoside combination than by 20 mg/kg
silymarin (in vitro).3161
LARCH
NEW
^ Larix spp. bark
Ia. 1) A randomized, double-blind parallel group of 45 adults used 4.5 grams of larch
arabinogalactan or maltodextrin placebo as a powder in water or juice once daily for 72 days to
test antibody response to Streptococcus pneumoniae pneumonia vaccine (PO in human study).
The 23-valent vaccine was given after 30 days, and 21 and 42 days later the pneumococcal
antigen-specific IgG antibodies subtypes 18C and 23F were increased significantly more in the
larch arabinogalactan group than in the placebo group, while subtypes 4, 6B, 9V, and 19F also
were greater with the larch group, but not significantly.2739 Larch arabinogalactan has been
shown to enhance human natural killer cell cytotoxicity indirectly by increasing release of
interferon gamma (in vitro)2754 and has reportedly been used clinically to enhance immune
function and thereby reduce the frequency and severity of recurrent pediatric otitis media
(empirical).2755
2) A randomized, placebo-controlled, double-blind 60-day study wth 75 healthy adults used 1.5
g/day larch arabinogalactans with 27, 4.5 g/day arabinogalactans with 25, and placebo with 23
and then administered an influenza vaccine and tetanus vaccine after 30 days (PO in human
clinical study). The Clostridium tetani toxoid IgG levels were significantly greater 30 days after
the vaccine for the 1.5 g/day dose than for placebo. There were no significant immunoglobulin or
adverse events differences between groups following the influenza vaccine.3351
LICORICE p. 225
*Glycyrrhiza glabra [or Glycyrrhiza uralensis] root/rhizome
Contraindications
4) Avoid use in pregnancy,2,4,6,17,401 especially excessive intake.1890
A study of 392 pregnant Italian women found that those 14 who were regular users of licorice
had a 35.7% higher frequency of threatened miscarriages, mostly in the 4th-5th month of
gestation, and a 16.7%% increase in preterm labors compared to non-users (PO in human
study).3078 In Korea, 185 women taking Chinese licorice (G. uralensis) at a maximum dose of 2.1
g/day during the first through 25th weeks of pregnancy to treat conditions such as coughs or colds
had a significantly higher rate of stillbirths, compared to 370 age-matched controls and to the
general population (PO in human study). Other outcomes between the 2 groups were similar,
suggesting Chinese licorice is not teratogenic.3332
Drug Interactions
Ia. ^ 3) When 17 patients with Addison's disease receiving cortisol were given 24 grams daily for 3
days of commercial licorice containing about 150 mg glycyrrhizin, the licorice significantly
increased median serum cortisol levels for 2.6 hours after licorice ingestion, with a 5.7% increase
of cortisol bioavailability over that time (PO in human clinical study). The median urinary
cortisol/cortisone ratio was also significantly increased.3021
53
Ib. + 5) An 80-year-old woman on warfarin twice developed elevated INR and black tarry stools after
eating a pound of licorice candy (PO in human case report). Her INR was raised from a baseline
of 2.1 to 5.5 after licorice consumption; 2 weeks after being advised to restrict licorice, her INR
decreased to 1.2.3446
Decreased coagulation following excessive licorice consumption may be possible due to
inhibition of thrombin by glycyrrhizin, shown to prolong plasma thrombin and fibrinogen clotting
times and to inhibit thrombin-induced platelet aggregation (in vitro).3447 [This seems likely, since
enhanced metabolic breakdown of S-warfarin was induced by 500 mg/kg of an aqueous extract
equivalent to 3 gm/kg dried root (PO in rats), probably through activation of pregnane X receptor
as shown by an ethanolic extract of G. uralensis (in vitro).1926 Such an impact on warfarin
metabolism would actually lower the INR.]
II. + 3) The ethanolic extract of G. uralensis root at 1000 mg/kg with a hypnotic dose of
pentobarbital significantly increased sleep duration and at 500 and 1000 mg/kg decreased sleep
latency (PO in mice). The extract showed no sleep inducing effects of its own at 1000 mg/kg in
any of 15 animals but induced sleep in 80% given a subhypnotic dose of pentobarbital (PO in
mice). It also displaced flumazenil from the GABAA-BZD receptor by 98% at 10 mg/ml (in
vitro).3127
+ 4) When the methanolic extract of licorice as given for 6 days at a dose of 1 g/kg before IV
administration of 150 mg/kg acetaminophen, the biliary and urinary excretions of the
acetaminophen-glucuronide was significantly increased by 156% and 132%, respectively (PO in
rats). The enzymatic activity of UDP-glucuronosyltransferase (UGT) was shown to increase by
111% at the same licorice extract dose, while concentration of UGT was increased 257%. This
indicates that licorice extract could increase liver detoxification of xenobiotics.558
Ia. 2) [Clarifications] After treating stomach ulcers for 12 weeks, DGL with 88% healing was
statistically as effective as cimetidine with 94% healing in groups of 50 patients of which 28 in
the licorice group consumed ethanol and 7 recently used prednisone or NSAIDs (PO in human
clinical study). Though ulcerations and symptoms associated with anti-inflammatory use were
more severe, recent anti-inflammatory drugs intake or habitual alcohol consumption did not
influence the rate of ulcer healing.502
IIa. 3) Coating ibuprofen with licorice extracts reduced stomach ulcers and lowered the ulcer index
compared to use of ibuprofen alone (PO in rats).1006
Similarly, an hour before being given a stomach ulcer-inducing dose of indomethacin,
licorice extract doses of 12.5,25, and 50 mg/kg were administered; all doses significantly reduced
the ulcer index compared to indomethacin alone, while raising the gastric pH (PO in rats).2976
LOBELIA p. 231
*Lobelia inflata herb or seeds
Ia. 1) A lobelia alkaloid mixture or 8 mg lobeline reduces tobacco consumption as a cigarette
smoking deterrent (PO in human clinical study).554
In a study of 22 smokers who smoked on average 31.5 cigarettes daily, tablets with either 2.5,
5.0, or 7.5 mg were given sublingually 3, 6, 9, or 12 times daily beginning the day after stopping
smoking at noon (PO in human clinical study). Withdrawal symptoms were significantly reduced
with increasing cumulative dosage, with maximum effectiveness with 7.5 mg taken either 9 or 12
times per day. Adverse effects were not clinically significant.3453 In a randomized, placebo-
controlled, double-blind trial with 180 healthy smokers, 90 were given 7.5 mg of lobeline
sublingually 9 times daily for 6 weeks (PO in human clinical study). Among smokers who were
highly dependent on tobacco that completed the trial, there was a greater tendency to cease
smoking among those who used lobelia versus placebo.3454
54
LONG PEPPER p. 232
Piper longum fruit
Drug Interactions
Ia. + 4) A single dose of the potent non-nucleoside inhibitor of HIV-1 reverse transcriptase,
nevirapine [a CYP 3A substrate] had 120% greater maximum concentration and 170% increased
bioavailability in 8 healthy subjects when taken after 6 days of piperine compared to placebo in a
crossover trial (PO in human study).3132
Ia. 1) Piperine increased serum concentrations of curcumin and increased curcumin bioavailability
by 2000% (PO in human study).1533
The significant improvements by 200 mg/kg oral curcumin of chronic stress impaired memory
performance and serum cortisone, along with oxidative stress parameters including elevated
malondialdehyde and decreases in reduced glutathione, superoxide dismutase and catalase, were
significantly enhanced with the addition of 20 mg/kg piperine (PO in rats).3396
IIa. + 1) Piperine at 70 mol/kg increased plasma bioavailability of the chemopreventive agent
epigallocatechin gallate [EGCG] in green tea by 1.3-fold when given concurrently compared to
EGCG given alone (PO in mice). Piperine also increased the maximum plasma concentration of
EGCG by inhibiting glucuronidation in mice intestines by 40%. Likewise, the gluruonidation of
EGCG was inhibited in human HT-29 colon adenocarcinoma cells (in vitro). Piperine also
increased EGCG transit time in the intestines (PO in mice).2935
addition of 0.02g% of piperine to the diet, compared to the same diet without piperine (PO in
rats). Calcium absorption was improved the most. Piperine increased the uptake of calcium better
than either capsaicin or ginger.3471
LYCIUM p. 234
Lycium barbarum berry
(Barbary wolfberry, Chinese wolfberry, goji)
Drug Interactions
Ib. 1) After 4 days of drinking a concentrated decoction of 5 g of the fruit 3 to 4 times daily, a 61-
year-old woman stabilized on warfarin experienced an INR elevation from 2.4 determined 4
weeks prior to 4.1 just after the lycium consumption (PO in human case report). After
discontinuing the tea and stopping warfarin for 1 day and restarting it at a lower weekly dose, 7
days later her INR was 2.4 and remained stable for 7 subsequent tests over the next 3 months.
After various concentrations of the drug and herb were incubated with microsomes to assess
potential inhibition of CYP 2C9 metabolism of warfarin, no inhibition was observed (in vitro).1768
In another incident, an 80-year-old woman on a chronic stable warfarin dosage had her
therapeutic 2-3.5 INR elevated twice after drinking lycium tea (PO in human case report). On the
first occasion, 3 cups of tea made from 10 g lycium fruit per cup the first day was followed by 2
cups of tea the second day, raising her INR to 4.97. Two months later after restabilizing the INR,
she consumed 4 cups of the tea 1 day prior to testing, and her INR was raised again to 3.86. Other
possible interferences with INR were excluded.3027 A third case involved a 71-year-old woman
taking warfarin who was hospitalized with a greatly elevated INR and prothrombin time >120
seconds after drinking goji juice for 4 days (PO in human case report). She was experiencing a
bloody nose, bruising, and rectal bleeding. After 2 days off of warfarin and goji juice, along with
phytonadione treatment, her INR was reduced to 2.6. The Naranjo probability scale indicated the
INR elevation was due to a probable interaction between the juice and warfarin.3448
IIa. + 1) The ascites, oxidative stress, and cardiotoxicity produced by the chemotherapy agent
doxorubicin weekly for 3 weeks was significantly reduced by prior and ongoing daily
consumption of lycium berry decoction (PO in rats). Mortality was lowered from 38% to 13%,
55
the cardiotoxicity showed significant reduction in conduction abnormalities, loss of heart muscle,
and arrhythmia, while the significantly increased superoxide dismutase and lowered lipid
peroxidation and serum AST demonstrated less oxidative stress in those given lycium extract.
Lycium extract did not interfere with doxorubicin cytotoxicity (in vitro).3029
When goji polysaccharides were given at 200 mg/kg for 7 days before and 3 days after 10
mg/kg intravenous doxorubicin, the drug's testicular toxicity was dramatically reduced compared
to controls given water (PO in rats). The polysaccharides reduced oxidation markers and
increased plasma testosterone levels. Compared to controls, the severe degenerative changes to
seminiferous tubules and abnormal sperm rate was attentuated, and reductions of testicular
weight, sperm concentrations, and mobile sperm percentage were ameliorated.3110
+ 2) The polysaccharide fraction given at a dose of 200 mg/kg daily for 6 days following 2 days of
myelosuppression by mitomycin C injections led to significantly enhanced recovery of platelet
counts and volume and peripheral red blood cell counts, hemoglobin, and hematocrit from 10 to
21 days following the drug (SC in mice).3030
MACA p. 235
Lepidium meyenii root
(Peruvian ginseng)
Ia. 1) In a randomized double-blind 12-week trial on 14 women and 2 men with sexual dysfunction
resulting from use of SSRIs to treat depression, the 9 taking 3 gr/day of maca had increased
sexual function scores (PO in human clinical trial).2486
A 12-week, placebo-controlled, double-blind study of 30 premenopausal and 12
postmenopausal women with sexual dysfunction induced by SSRIs or venlafaxine (a serotonin
and norepinephrine re-uptake inhibitor [SNRI]) utilized 3 grams daily maca root in half (PO in
human clinical study). Remission rates were almost twice as high for maca as placebo in the
Arizona Sexual Functioning Scale [score ≤10] and the Massachusetts General Hospital Sexual
Function Questionairre [score ≤8]. The higher remission rates occurred primarily in
postmenopausal women.3483
MAITAKE p. 236
Grifola frondosa mushroom fruiting bodies
Ia. + 1) 750 mg of maitake mushroom powder plus 54 mg of its glycoprotein fraction designated MSX
3 times daily between meals was used by 26 randomized polycystic ovary syndrome patients for
up to 12 weeks, while clomiphene citrate was given to 31 others; 15 of those who did not
respond to these monotherapies were given a combination of the two for up to 16 weeks (PO in
human clinical study). The ovulation rates were 77% for maitake/MSX patients and 94% for
clomiphene patients. Of those nonresponders given the combination, evidence of ovulation was
shown by 7 of 7 of those who failed with maitake/MSX and 6 of 8 of those who failed with
clomiphene.2910
Ib. + 1) When 4 patients with liver carcinoma were given 40-150 mg of maitake MD-fraction and 4-6
g of whole maitake powder in conjunction with 5-fluorouracil chemotherapy and/or after
treatment with cisplatin and/or adriamycin, in all 4 cases the cancer either disappeared,
improved, or stabilized with the addition of the maitake (PO in human case series). Similar
outcomes were reported with single cases of breast and lung cancers with metastases. These 6
cases were described as representative of 36 cancer patients in which significant symptom
improvement or regression was observed for 11/16 with breast cancer, 7/12 with liver cancer, and
5/8 with liver cancer with maitake use. Immune function improvements with interleukin (IL)-2
production and CD4+ count were noted in these cancer after addition of maitake and its MD-
fraction, compared to a lack of improvement in these factors in 3 leukemia patients.3341
56
MILK THISTLE p. 243
Silybum marianum = Carduus marianus seeds
Drug Interactions
Ia. + 3) The inhibition of losartan metabolism by treatment with 140 mg of silymarin 3 times daily
for 14 days was only significant in the 6 Chinese men with a CYP2C9*1 genotype (PO in human
study). Though it was not significant in the 6 men with a CYP2C9*3 genotype, the active
metabolite E-3174 was reduced in both genotypes, so it had the effect of potentially diminishing
the therapeutic efficacy of taking losartan as an antihypertensive for both genotypes.2981 Based on
clinical relevance, the pharmacokinetic interaction risk has been assessed as low (speculative).3222
+ 4) In a single-blind, placebo-controlled, randomized crossover trial, silymarin at 420 mg daily for
14 days inhibits Pgp efflux of 1 dose of talinolol in 18 healthy subjects, 6 each of which were
homozygous (CC, TT) and heterozygous (CT) for MDR1 3435 (PO in human study). The peak
plasma concentration and bioavailability were both significantly higher after silymarin by 36.2%
and 36.5%, respectively, while the oral clearance was significantly lowered by 23.1%, compared
with placebo.3137
HOWEVER, when tested with the Pgp substrate digoxin in 16 healthy humans 440 mg
silymarin given as 900 mg of standardized extract daily for 14 days did not significantly alter the
drug bioavailability. There was a tendency toward reducing digoxin levels, suggesting potential
Pgp induction.1806 Based on clinical relevance, the pharmacokinetic interaction risk has been
assessed as low (speculative).3222
III. 2) S(-)-warfarin 7-hydroxylation by CYP 2C9 was competitively inhibited by silybin (in
vitro).1297
Silybin B with an IC50 of 8.2 M was a more potent inhibitor of human liver microsome
CYP2C9 warfarin metabolism than silybin A with an IC50 of 18 M (in vitro). Isosilybins A and
B were less potent still with respective IC50s of 74 and >100 M. Silybin B also significantly
inhibited recombinant CYP 2C9*1 and its recombinant polymorphisms 2C9*2 and 2C9*3 more
than silybin A (in vitro). Both silybins inhibited CYP2C9*3 significantly more than the CYP2C9
of human liver microsomes pooled from 50 donors.2980
Ia. 2) 420 mg silymarin daily given to alcohol cirrhosis patients for several years reduced the
mortality rate (PO in human clinical studies).495,1256
HOWEVER, in randomized, multicenter, double-blind trial with 200 alcoholics with cirrhosis,
450 mg of silymarin did not improve survival time compared with placebo (PO in human clinical
study).2825
Silymarin use following ethanol hepatotoxicity helps normalize lab indices for transaminases
(PO in human clinical studies).119,1257
Silymarin at 200 mg/kg given with 5 g/kg ethanol 3 times in 24 hours attenuated the acute
elevation in serum ALT, enhance lipid peroxidation, increase in liver TNF production, decrease
in glutathione content, and microvesicular steatosis with mild necrosis caused by ethanol given
alone (PO in mice).2901 Silymarin at 60 mg/kg for 24 weeks concurrently with ethanol
significantly and dose-dependently increased serum levels of alcohol dehydrogenase (ADH) and
ALDH and decreased liver levels of CYPs 1A2, 2E1, and 3A induced by ethanol taken without
silymarin (PO in rats).3283
4) Silymarin given to diabetes type 2 patients taking metformin and glibenclamide
significantly decreased glycosylated hemoglobin, fasting blood sugar, total cholesterol, LDL,
triglycerides, and SGOT and SGPT levels, compared to placebo (PO in human clinical study).2041
A randomized, placebo-controlled, triple-blind parallel trial with 40 type 2 diabetes patients
receiving metformin and/or glibenclamide utilized 140 mg of silymarin 3 times daily with 20
patients for 45 days to observe the impact on oxidative stress and inflammatory markers (PO in
human clinical study). Those receiving the silymarin increased significantly their total antioxidant
capacity and superoxide dismutase and glutathione peroxidase activities by 8.4%, 12.9%, and
57
30.3%, respectively, compared to those receiving placebo, along with a significant 26.8%
reduction in high sensitivity C-reactive protein. In addition, fasting blood sugar was decreased
significantly by the silymarin treatment, compared to placebo.3479
IIa. 1) Prevention by silybin of hepatotoxicity from acetaminophen protected from glutathione
depletion and lipid peroxidation (IV in rats).117
Giving silymarin 30 mg/kg with, or 4 hours after, a hepatotoxic dose of 150 mg/kg of
acetaminophen prevented the associated elevations in serum ALT, AST, ALP, LDH, total and
direct bilirubin, and methemoglobin equivalent to the effects of 100 mg/kg of N-acetylcysteine
(PO in cats).2824 When silymarin was given at 100 mg/kg body weight after acetaminophen-
induced hepatotoxicity, improvements in albumin globlulin ratio and serum alkaline phosphatase
and transaminases AST and ALT were significantly better (PO in rats). Also, the histopathologic
damage to the liver was less and signs of regeneration were greater than with no treatment.3181
DNA strand breaks in liver cells caused by 25-30 mM acetaminophen were prevented by silybin
at 25 mcM, though hepatocellular toxicity of acetaminophen was not affected (in vitro).2902
3) Silybin helps prevent kidney damage from nephrotoxic cisplatin at doses of 200 mg/kg (IV
in rats).186,187
HOWEVER, in a randomized, placebo-controlled, double-blind trial silymarin at 420 mg daily
beginning 24-48 hours before and continuing through three 21-day cisplatin chemotherapy
courses did not reduce acute kidney injury or renal wasting of magnesium and potassium
electrolytes in 12 patients, compared to 12 patient controls (PO in human clinical study). No
adverse effects were associated with silymarin use.3536
OAT p. 252
Avena sativa bran
Drug Interactions
Ib. 1) 50-100 gm daily in 2 patients taking lovastatin resulted in elevated LDL that decreased after
oat bran was withdrawn (PO in human case reports).1841
HOWEVER, in randomized hypercholesterolemic subjects, consumption of only 6 gm oat
bran concentrate with 54% beta-glucan twice daily with meals for 6 weeks significantly lowered
LDL in 35 adults, compared to 40 controls (PO in human clinical trial).2972
OLIVE p. 253
Olea europaea fruit oil
Ia. 1) Consumption of 3-4 spoonsful of extra virgin olive oil daily for 6 months compared to
safflower oil in a crossover study led to significant reductions in the use of high blood pressure
medications including atenolol, nifedipine, lisinopril, doxazosin, and hydrochlorothiazide (PO
in human clinical study).1773 [CORRECTION Note: listed in early printings of the book as a Drug
Interaction.]
+ 2) In 34 type 2 diabetes patients with a single diabetic foot ulcer, olive oil was used on 17
patients in conjunction with routine care received by the other 17 patients that consisted of local
debridement, oral antibiotics, and daily cleansing and sterile dressing (TP in human clinical
study). The oil was poured on the ulcer surface with a syringe and then a gauze bandage soaked
with the oil was applied to the ulcer daily for 4 weeks. After 4 weeks the olive oil group had
singificant improvements in degree of ulceration, color, surrounding tissue, and total ulcer status,
compared to the control group. The ulcer area and depth were also significantly improved in
comparison to controls. Complete healing of ulcers occurred in 73.3% of olive oil users versus
13.3% of non-users, a significantly greater percentage.3500
OREGON GRAPE p. 254
58
Mahonia spp. root bark
Contraindications
I. 5) [Note CORRECTION: This item should be listed as 3) under DRUG INTERACTIONS Ia. on
the next page (p. 255). See below.]
II. 3) Avoid in jaundice in newborns777,1890 or from hemolytic anemia or unconjugated
hyperbilirubinemia as Gilbert’s syndrome and Crigler-Najjar syndrome (speculative).777
Drug Interactions
Ia. 1) [CORRECTION: See appropriate listing for berbamine under Complementary Adjuncts Ia. 3.]
Berberine at 300 mg 3 times daily for 14 days in 17 healthy males significantly increased the
3) The combination of 500 mg berberine 3 times daily for 3 months in 43 patients with poorly-
controlled type 2 diabetes together with one or more of their regular oral hypoglycemic
medications including sulfonylureas in 28, metformin in 20 acarbose in 15, and/or insulin in 10
resulted in lower fasting and postprandial blood sugar from week 1 through week 12 (PO in
human clinical study). Fasting plasma insulin was also lowered by 28% and an index of insulin
resistance by 45% of those on medications, while total cholesterol and LDL were likewise
reduced. In 31 newly diagnosed type 2 diabetics to whom 15 were given the same dose of
berberine and 16 used 500 mg metformin 3 times daily, berberine’s hypoglycemic effect was
similar to that of metformin on fasting and postprandial blood glucose, as well as reducing
glycosylated hemoglobin and plasma triglycerides (PO in human clinical study). Transient
gastrointestinal adverse effects were experienced by 35% of the patients, or 20 in total.2315
study).3238
59
study).2907
When the same doses of berberine and plant stanols were used with a normal diet for 4 weeks, the
(speculative).2753
60
by doxorubicin.3148
PASSION FLOWER p. 258

Passiflora incarnata herb
Ia. 2) [See Ib. 1) in book.] A combination of 3 herbal hydroethanolic extracts including passion
flower herb 4-7:1, hops (Humulus lupulus) strobiles 4-8:1, and valerian (Valerian officinalis) root
3-6:1, was found to markedly improve symptoms associated with benzodiazepine withdrawal
phase in 107 patients of an average age of 54 years (PO in human clinical study). The extracts
were begun with 1-2 tablets daily as benzodiazepine dosage was reduced for 2 weeks, and
continued for the next 4 weeks after benzodiazepine use was stopped. Improvement was shown
for pronounced tiredness in 76% and general unrest in 71%, according to subjective assessment
of patients. Sleep improved in 68% by the end of the treatment, and 74% had more motivation
and drive than at the beginning. At the end, 62% were calmer and better able to cope. No adverse
drug events occurred in any patients.2634
PAU D’ARCO
Tabebuia avellanedae = Tabebuia impetiginosa bark
Drug Interactions
III. + 3) Though not genotoxic itself, the bark potentiated the genotoxicity of the chemotherapy
mutagenic drug doxorubicin (in vitro).3296
PELARGONIUM NEW
^ Pelargonium sidoides root
Ia. 1) Of 200 adult patients with chronic obstructive pulmonary disease [COPD] using salmeterol
as regular inhalant therapy, or this combined with budesonide, along with ipratropiumbromide
and fenoterol as needed, 99 were also given 30 drops 3 times daily for 24 weeks a 1:8-10
hydroethanolic root extact while 100 received a matched placebo (PO in human clinical study).
The extract group on average significantly went a longer time before the first exacerbation, had
fewer exacerbations, used less of the antibiotics augmentin or ofloxacin and for shorter periods,
lost fewer work days, and had great patient satisfaction than did the placebo group. Aside from
more mild gastrointestinal disorders, the extract caused no more adverse effects than placebo.3269
PEPPERMINT p. 261
Mentha x piperita leaves
Drug Interactions
II. 3) Acute pretreatment with 0.2 ml/kg peppermint oil increased gut motility and significantly
prolonged pentobarbitone sleeping time, while 5-day pretreatment with the same dose
significantly shortened it (PO in mice). This could be due to short term inhibition and long-term
induction of pentobarbiton metabolism by the oil (speculative).3113
4) Chronic intake of 0.1-0.2 ml/kg peppermint oil significantly decreased the analgesic effect of
codeine (PO in mice). This could possibly be due to an inhibition of codeine conversion to
morphine by CYP 2D6 (speculative), but there was no acute effect.3113
5) Chronic intake of 0.2 ml/kg peppermint oil significantly prolonged and enhanced the impaired
coordination effect of midazolam (PO in mice). This was probably due to CYP 3A inhibition
over time (speculative), since there was no acute effect.3113
Ia. 1) When combined with the antiemetic drugs granistron, dexamethasone, or metoclopramide,
2 drops of peppermint or spearmint (Mentha spicata) oils given in capsules with sugar a half-hour
61
before and 4 and 8 hours after chemotherapy significantly reduced nausea and vomiting induced
by chemotherapy, compared to the drugs alone or the drugs with placebo, in a randomized
double-blind trial with 200 cancer patients (PO in human clinical study).3285
POMEGRANATE p. 266
Punica granatum fruit
Drug Interactions
Ib. 1) A man using ezetimibe daily and rosuvastatin every other day developed rhabdomyolysis
after beginning pomegranate juice (PO in human case report).1982
HOWEVER, prior to statin treatment he had elevated creatinine kinase, and taking
atorvastatin and simvastatin previously caused myalgia. All 3 statins additionally increased the
creatine kinase levels. Unlike atorvastatin and simvastatin that are metabolized by CYP 3A4,
rosuvastatin is metabolized by CYP 2C9 and 2C19.1982 Despite inhibiting the metabolism of CYP
2C9 drug substrates (in vitro3112,3245 and in rats3112), when 250 ml of pomegranate juice or a single
capsule with 1 gram pomegranate extract containing 689 mg of polyphenols was given in a
crossover trial to 12 subjects along with the CYP 2C9 substrate flurbiprofen, no change in its
metabolism was noted when compared with placebo control and the positive control inhibitor
fluconazole (PO in human study).3245 Also, though pomegranate juice has been shown to inhibit
CYP 3A (PO in rats,1920 in vitro1920,1923), [Note CORRECTION as follows.] it does not inhibit
metabolism of midazolam by CYP 3A4 (PO in humans).2213
2) [Note CORRECTION: this item is properly found as item IV. 1.]
II. + 2) Pomegranate juice given at 3 ml/kg/day as a pretreatment for 1 week led to significantly
increased absorption 5-fold of the calcium channel blocker nitrendipine (PO in rats). The drug's
peak plasma concentration and oral bioavailability also were significantly increased 1.8-fold
when the juice was administered 1 hour before nitrendipine. The effect is likely due to inhibition
of Pgp and CYP3A in the gut, but not in the liver. The elimination half-life was not altered by
pretreatment or concurrent use of the juice.3111
+ 3) When 3 ml pomegranate juice was given 1 hour before tolbutamide, the bioavailability
significantly increased 1.2-fold, but the elimination half-life was not altered (PO in rats). This
suggests that intestinal metabolism by CYP 2C9 was inhibited, but not its liver metabolism.3112
HOWEVER, despite also inhibiting the metabolism of CYP 2C9 drug substrates (in
vitro3112,3245), when 250 ml of pomegranate juice or a single pomegranate extract capsule with 689
mg of polyphenols was given in a crossover trial to 12 subjects along with the substrate
flurbiprofen, no change in its metabolism was noted when compared with placebo control and the
positive control inhibitor fluconazole (PO in human study).3245
III. 1) Pomegranate juice strongly inhibited the metabolism of the CYP 3A substrate midazolam (in
vitro).1923 Pomegranate juice was shown in other studies to inhibit CYP3A (in vitro,1920,2123,2213 in
rats1920).
HOWEVER, 2 doses of 8 oz juice each given about 12 hrs and 1 hr prior to midazolam had no
effect on IV or oral midazolam clearance (PO in human study).2213
+ 2) Pomegranate juice almost completely inhibits diclofenac metabolism by human liver
microsomes in a 5% concentration when 25 mcl is added (in vitro), indicative of CYP 2C9
inhibition.3112
HOWEVER, despite also inhibiting the metabolism of CYP 2C9 drug substrates (in vitro3245
and in rats3112), when 250 ml of pomegranate juice or a single pomegranate extract capsule with
689 mg of polyphenols was given in a crossover trial to 12 subjects along with the substrate
positive control inhibitor fluconazole (PO in human study).3245
IV. [1) A woman was stabilized on warfarin dosage for 5 months while consuming pomegranate
juice 2-3 times/week (PO in human case report) . She began to have subtherapeutic INRs for 4
months after skipping a couple of doses, but returned to normal dosing and INRs. After referral to
62
an anticoagulation clinic, she stopped the juice and had 2 normal INRs, but then 2 subnormal
INRs though any potential CYP inhibition by the juice would have been eliminated. Another dose
increase resulted in normal INRs.2602
HOWEVER, despite inhibiting the metabolism of CYP 2C9 drug substrates (in vitro3112,3245
and in rats3112), when 250 ml of pomegranate juice or a single pomegranate extract capsule with
689 mg of polyphenols was given in a crossover trial to 12 subjects along with the substrate
positive control inhibitor fluconazole (PO in human study).3245]
Ia. 1) Use of 10 ml daily of a pomegranate juice concentrate, with a polyphenol content of 1300 mg
equivalent to 200 ml of juice, for 12 weeks by 6 rheumatoid arthritis patients taking the
disease-modifying anti-rheumatic drugs methotrexate and hydroxychloroquine [plus sulfazine
in 2], along with prednisone in 5 and NSAIDs in 4, resulted in significantly fewer tender joints
that decreased by 62% (PO in human clinical study).3024
IIa. 1) The component ellagic acid at 60 mg/kg has been shown to reduce effects of alcohol
markers.3155
2) After 12 weeks, in groups inoculated in the tibial bone with metastatic prostate cancer cells
and treated with either the 50% DMSO vehicle as controls, or with 5 mg/kg docetaxel once
weekly, pomegranate fruit extract 60 mg/kg 3 times per week, or a combination of the docetaxel
and pomegranate extract treatments, the PSAs levels in these groups were 60.5, 54.1, 40.4, or
11.6 ng/ml, respectively (IP in mice). Besides the extract and combination groups having
significantly lower PSAs than the control or docetaxel groups, radiographically the extract and
combination groups also showed inhibitory effects of prostate cancer tumor growth in bones
compared to controls.3381
PRICKLY PEAR p. 269

Opuntia spp. stems/pads and fruit
Drug Interactions
Ia. 1) Heated and unheated stems of the species Opuntia ficus-indica given at a dose 500 gm to 8
type diabetics receiveing glibenclamide (glyburide) lowered blood sugar after 2-3 hours (PO in
O. ficus-indica water extract of the stems and a proprietary skin blend of the 3 parts stem to 1
part fruit both significantly reduced blood glucose and increased insulin in a 120 minute glucose
tolerance test in normal animals at doses of 6 mg/kg, while the skin blend also significantly
increased basal insulin levels (PO in rat study).2826
IIa. 1) Freeze-dried pads given before 90% ethanol to assess stomach ulcer formation significantly
reduced hyperemia and lesions (PO in rats).2696
When 5 mg/kg of prickly pear mucilage was given after chronic gastric damage from ethanol,
the enzymatic changes and mucosal erosion were promptly corrected by its anti-inflammatory
effect (PO in rats).3505
PSYLLIUM p. 270
Plantago psyllium = Plantago afra and Plantago ovata = Plantago ispaghula seed or seed husk
Ia. 2) In diabetes type 2 psyllium reduces glucose concentration in the blood when taken with
glibenclamide [glyburide] (PO in human clinical study).1448
63
In a 3-part randomized crossover study with 7 type 2 diabetic patients using glibenclamide and 5
taking tolbutamide, the use of 15 g of psyllium before 90 g of white bread reduced postprandial
glucose significantly compared to placebo and similarly to acarbose (PO in human clinical
study).2798 A randomized, double-blind, placebo-controlled 8-week study of 5.1 g psyllium in 250
ml twice daily before breakfast and dinner in 36 type 2 diabetic patients taking glibenclamide or
metformin led to significant decreases in fasting blood sugar, glycosylated hemoglobin, and
LDL/HDL ratio and a significant increase in HDL-cholesterol with psyllium compared to placebo
(PO in human clinical trial). Gastric tolerance of metformin was better in the psyllium group.2799
Another randomized, blinded, placebo-controlled 8-week study with 29 type 2 diabetic patients
using diet and oral sulfonylureas or diet only showed significantly reduced all-day and
postprandial blood blood glucose, total cholesterol, and LDL-cholesterol with 5.1 g psyllium
before the morning and evening meals compared to placebo (PO in human clinical trial).2800 In 12
type 2 diabetics taking unspecified oral hypoglycemic drugs and 6 treating with diet alone, 6.8 g
psyllium twice daily before the first and last meal reduced maximum postprandial glucose
elevation significantly after all 3 meals (PO in human clinical study). There was no significant
difference in this effect from those who used the drugs compared to those who did not.2801
QUASSIA (SURINAM) p. 272

Quassia amara bark, wood, root
(bitterwood, Surinam wood; Sp.: amargo, cuassia, hombre grande, palo muneco, ruda, Simaruba;
Port.: pau amarelo, guabo, pau quassia, wewe gifi)
IIa. + 1) For preventing gastric ulcers induced by 40 mg/kg i.p. indomethacin, 200-800 mg/kg of a
quassia methanolic extract was found to significantly reduce the incidence by 77-85% (PO in
rats). Gastric acidity also decreased dose-dependently. Quassia extract at 20 mg/kg inhibits basal
and histamine-induced gastric acid secretion which is accentuated by cimetadine. Quassia
probable acts through histamine H2 receptor.3382 Gastric ulcers induced by either indomethacin or
by ethanol were significantly reduced by doses of 4.9-48.9 mg/kg daily for 1 week of an extract
containing quassinoids (PO in rats).3383 In gastric ulcers induced by a combination of
indomethacin with the cholinomimetic bethanechol, 100 mg/kg of extracts made with either 70%
or 100% ethanolic, dichloromethane, or hexane reduced ulcer incidence by 22.5%, 23.4%, 50.5%
and 46.8%, respectively (PO in mice). For ulcers induced by combined hydrochloric acid and
ethanol the same 4 extracts significantly reduced ulcer formation at doses of 25 (except 70%
ethanolic extract), 50, 75, and 100 mg/kg and significantly increased free mucus.3384
RASPBERRY p. 273
Rubus idaeus leaves
IIa. + 1) The component ellagic acid at 60 mg/kg has been shown to reduce effects of alcohol
markers.3155
ROMAN CHAMOMILE p. 276

Chamaemelum nobile = Anthemis nobilis flowers and herb
Contraindications
I. 1) Avoid in pregnancy, due to the emmenogogue and abortifacient effects of the flower and of
the plant (empirical)74,150,1125 and its volatile oil.74 Regular internal consumption should be
avoided throughout pregnancy, based on a study of 392 pregnant Italian women that found the
37 who were regular users of chamomile had a 21.6% higher frequency of threatened
64
miscarriages and a 21.6% increase in preterm labors, compared to non-users (PO in human
study).3078
HOWEVER, the authors failed to identify by scientific name whether the chamomile used was
German (Matricaria recutita) or Roman (Chamaemelum nobile) chamomile.3078
ROSEMARY p. 276
Rosmarinus officinalis leaves
IIa. 1) Aqueous and ethanolic extracts of the aerial parts reduced the withdrawal syndrome of
morphine when given at 1.7 g/kg and 1.0 g/kg, respectively (IP in mice). Only the aqueous
extract contained an alkaloid. The extracts also reduced the analgesic activity of morphine.3464
SAFFRON p. 278
*Crocus sativus stigma
Ia. + 1) In a randomized, prospective, comparative pilot study with 34 patients with stable primary
open-angle glaucoma receiving treatment with timolol and dorzolamide eye drops, 17 also
received 30 mg aqueous saffron extract daily for 1 month (PO in human clinical study). During,
at the end of, and after a 1-month washout following the trial, intraocular pressure was measured
and compared between the 2 groups. The saffron group had a significant reduction of intraocular
pressure after 3 and 4 weeks compared to control group, but at the end of the was washout period,
both groups had returned to baseline levels. No adverse effects were encountered.3437
+ 2) A randomized, placebo-controlled, double-blind trial with 34 women with sexual dysfunction
from treatment of depression with fluoxetine used 30 mg of saffron daily with half of them for 4
weeks (PO in human clinical study). Those taking saffron had significant improvements after 4
weeks in the Female Sexual Function Index total score and subscore domains for arousal,
lubrication, and pain. Side effects for the 2 groups were similar.3480 Similarly, a randomized,
double-blind, placebo-controlled study of 30 men with erectile dysfunction from treatment of
depression with fluoxetine utilized 30 mg daily of saffron with 15 of these men for 4 weeks (PO
in human clinical study). After 2 weeks and 4 weeks, there were significant improvements in the
total score for the International Index of Erectile Function scale as well as with the domains for
erectile function and sexual satisfaction. A total of 60% of the men using saffron regained normal
erectile function, compaired to 7% of the men on placebo; side effects were similar in both
groups.3481
In a pilot study for men with idiopathic erectile dysfunction, 20 men with ED took a 200 mg
tablet of saffron each morning for 10 days (PO in human clinical study). After 10 days there was
significant improved nocturnal ridgidity and tumescence of both the tip and base of the penis,
along with significantly higher scores in the International Index of Erectile Function
questionnaire, both total score and in all domains: erectile function, sexual desire, intercourse,
orgasmic function, and satisfaction.3482
IIa. 1) The aqueous and ethanolic extracts of the stigma reduced the withdrawal syndrome from
morphine at doses of 80 and 800 mg/kg, respectively, whereas the constituent crocin did not (IP
in mice).3465
SAGE p. 279
*Salvia officinalis leaves
IIa. + 2) Sage hydroalcoholic extract, given at 100 mg/kg after and with IV vincristine for 10 of 12
days before formalin injection, reduced the second phase neuropathic pain expressions from
vincristine-induced peripheral neuropathy (IP in mice). The sage extract given alone also reduced
65
the formalin-exacerbated pain that was increased when vincristine was given alone (IP in
mice).3372
SANCHI GINSENG NEW

^ Panax notoginseng
(tienchi ginseng; Ch.: san qui ginseng,)
Ia. 1) In 140 patients with acute or subacute anterior cerebral ischemic stroke, 50 mg aspirin with
or without 100 mg of panaxatriol saponin extract standardized to ginsengosides [50% Rg1, 6%
Re] and notoginsenoside R1 [11%] was given daily for 4 weeks (PO in human clinical study).
Those receiving the extract had significantly better improvement in neurological function
involving movement of limbs and in daily living activities compared with aspirin alone. Adverse
events were equivalent between groups.3076
2) In a randomized study of 84 rheumatoid arthritis patients receiving diclofenac,
leflunomide, and prednisone for 28 days, 43 also received a total saponin fraction from sanchi
ginseng (PO in human clinical study). The clinical improvement were significantly better in the
saponin group for joint pain, tenderness, and swelling and time of morning stiffness compared to
using only drugs, even though the improvements were significant for the drugs alone. Also,
laboratory findings for the saponin group that were significantly better than for drugs-only
included lowered platelet count, ceruloplasmin, alpha1-acid glycoprotein, and C-reactive protein;
these were also lowered significantly for drugs alone, along with other rheumatoid arthritis
markers in both groups.3418
SAW PALMETTO p. 280

Serenoa repens fruit
Ia. + 1) A product with 320 mg saw palmetto extract, 5 mg lycopene and 50 mcg selenium was given
for 1 year with or without 0.4 mg of the adrenergic alpha-blocker drug tamsulosin and compared
with the effects of 0.4 mg tamsulosin alone in 219 men with benign prostatic hyperplasia and
lower urinary tract symptoms (PO in human clinical study). Those receiving the saw palmetto
extract/nutrients/drug combination had significantly greater improvement for International
Prostate Symptom Score (IPSS) and in maximum urinary flow than with tamsulosin alone or the
extract/nutrients alone after a year. The combination extract/nutrients/drug also improved erectile
dysfunction symptoms better than tamsulosin alone after 1 year.3411
However, a prospective study comparing 320 mg daily of saw palmetto extract with 0.4 mg
per day of tamsulosin or a combination of the 2 agents in groups of 20 patients each found no
statistical differences between the groupos in IPSS or maximal flow rates (PO in human clinical
study). The saw palmetto group had showed no adverse treatment effects.3434 Also, in a 6-month
randomized trial with patients with benign prostatic hyperplasia having lower urinary tract
symptoms in which 87 received 0.4 mg tamsulosin, 97 took 320 mg saw palmetto ethanolic
extract, and 81 used a combination of both, there were no statistical differences in outcomes
between the 3 groups (PO in human clinical study). All groups had significant improvements in
IPSS and maximal flow rates, with the saw palmetto group having the greatest decrease in IPSS
and the combination showing the greatest increase in flow rate. Treatment-related adverse effects
occured in 23% given tamsulosin alone and in 21% given the combination, but none were
observed in the group taking saw palmetto extract alone.3419
+ 2) A tablet with 320 mg saw palmetto extract, 200 mg Lactobacillus sporogenes, and 100 arbutin
was given daily for 30 days to 77 men with chronic bacterial prostatitis together with 600
mg/day the antibiotic prulifloxacin given for 21 days and compared with a prulifloxacin-only
regimen (PO in human clinical study). After 2 months, those who only received antibiotic had a
27.6% recurrence, compared to only 7.8% of those who also took the saw palmetto combination.
66
After 2, 4, and 6 months the prostatitis symptoms were significantly less among those receiving
saw palmetto combination with prulifloxacin, compared to those receiving prulifloxacin alone.3414
SCHISANDRA p. 281
Schisandra chinensis fruit
(northern schizandra Ch.: bei wu wei zi [Mand.])
Drug Interactions
Ia. 1) When 12 subjects took 600 mg extract daily for 14 days, it significantly increased talinolol
bioavailability, due to inhibition of P-glycoprotein efflux (PO in human study). The
bioavailability and peak plasma concentration of talinolol were significantly increased by
schisandra extract by 47% and 51%, respectively.3138 Based on clinical relevance, the
pharmacokinetic interaction risk has been assessed as high (speculative).3222
II. + 3) The lignan extract containing 10.9% schisandrol A, 2.4% gomisin C, 1.9% deoxyschizandrin,
and 1.8% -schizandrin inhibits intestinal CYP 3A4 metabolism of midazolam when a single 150
mg/kg dose is given with oral midazolam, but not hepatic metabolism for IV midazolam (PO in
rats). The lignan extract also inhibits metabolism of midazolam (in vitro).2832
HOWEVER, when 150 mg/kg of the lignan extract is given for 14 days, it induces the CYP
3A4 protein expression in the liver 2.5-fold and its intestinal metabolism 4-fold, and thereby
increases midazolam metabolism, especially in the small intestines (PO in rats). In those rats that
in which the extract and midazolam were co-administered after 14 of the extract, the induction
was modified somewhat by concurrent intestinal CYP 3A4 inhibition. Gomisin C was the most
potent inhibitor (in vitro) and the least concentrated in the liver (PO in rats), while schisadrol A
was the least potent (in vitro) and the most concentrated in the liver (PO in rats).2832
III. 1) While gomisins B and G are also active, gomisin C is the most potent inhibitor of CYP3A4
metabolism of erythromycin and testosterone and irreversibly inactivates it in a time- and
concentration-dependent manner (in vitro).2946
SCOTCH BROOM p. 282

*Cytisus scoparius syn. Sarothamnus scoparius tops
Ia. 1) In a randomized, placebo-controlled, double-blind trial to stop smoking tobacco, placebo or
cytisine from Cytisus spp. was given to 370 smokers each for 25 days (PO in human clinical
study). With minimal counseling while using 6 tablets with 1.5 mg cytisine each for 3 days, 5 for
9 days, 4 for 4 days, 3 for 4 days, and 2 tablets for the last 5 days, day 5 was the target quit day.
After 12 months from the end of treatment, significantly more [8.4%] of those receiving cytisine
were still abstaining, compared to the placebo group [2.4%]. The relative inexpense of cytisine
over other methods to stop smoking add to its appeal.3405
SHIITAKE NEW
^ Lentinula edodes (= Lentinus edodes) mycelia
Ia. 1) A mycelial extract at 1.8 grams daily was tested for 4 weeks to see its effect on quality of life
and the immune response of 7 cancer patients on chemotherapy, 3 with breast cancer receiving
epirubicin and cyclophosphamide and 4 with gastrointestinal (GI cancer) treated with TS-1,
UFT or 5-fluorouracil, irinotecan, and folate (PO in human clinical study). A first course
chemotherapy-only was compared to the second course combined with the extract. After the
second course there were significant improvements in quality of life, natural killer cell activity,
and immunosuppressive acidic protein levels. No adverse effects were found with the combined
extract and chemotherapy.3502
2) The mycelia extract was tested in 7 patients with advanced colorectal cancer and metastasis
and 1 with gastric cancer and metastasis during a second round of chemotherapy with irinotecan,
67
UFT, mitomycin C, 5-fluorouracil, levofolinate, and/or taxol (PO in human study). After the
first course of chemotherapy without the extract, adverse events of grade 1 or 2 had occurred in 6
of the 8 patients, but none occurred after the second course while using the extract. After the
second course there was also a tendency for improved interferon- production by CD4+ and
CD8+ T cells and CD56+ natural killer T cells.3503
SILK TREE p. 286

Albizia julibrissin bark
Drug Interactions
II. + 1) The ethanolic extract of the bark at 500 and 1000 mg/kg with a hypnotic dose of
pentobarbital increased sleep duration and decreased sleep latency (PO in mice). The extract
showed no sleep inducing effects of its own at 1000 mg/kg in any of 15 animals but induced sleep
in 67% given a subhypnotic dose of pentobarbital (PO in mice). It also displaced mesulergine
from the 5-HT2C receptor by 88% at 10 mg/ml (in vitro).3127
SOUTHERN SCHISANDRA NEW

^ Schisandra sphenanthera fruit
(southern schizandra; Ch.: nan wu wei zi)
Drug Interactions
Ia. 1) When 12 healthy subjects were given 3 capsules of extract with 11.25 mg deoxyschizandrin
per capsule twice daily for 14 days, preceeded and followed by a dose of tacrolimus, the
bioavailability, maximum blood concentration, and time to maximum concentration of tacrolimus
were significantly increased, while apparent oral clearance was significantly decreased (PO in
human study).2829
This was confirmed by examining first-pass metabolism in the intestines and liver, in which
oral bioavailability was significantly increased by 2.1-fold, largely due to intestinal first-pass
effect (PO in rats). The efflux transport of tacrolimus by Pgp was significantly lower with extract
exposure and CYP3A metabolism by rat and human liver microsomes was inhibited by 100 mcM
of extract (in vitro), indicating Pgp and CYP3A inhibition.2830 A tissue distribution study showed
that the tacrolimus was increased in the blood by 3-fold, as well as significantly increased in
muscle and and spleen, after 0.25 g/kg/day of the extract was taken for 4 days, compared to no
extract intake (PO in rats).2828
3) When 3 capsules of the extract were given twice daily [66.5 mg deoxyschizandrin/day] for 7
days, it significantly increased the oral bioavailability and maximum plasma concentration of
midazolam, compared to baseline levels (PO in human study). Midazolam half-life was
unchanged, but time to maximum concentration of midazolam and its metabolite 1'-hydroxy-
midazolam were significantly increased.3136
II. 1) An ethanol fraction of the fruit dose-dependently reduced sleep latency and increased sleeping
time induced by pentobarbital (PO in mice).2074
2) When 0.25 g/kg of an ethanolic extract was given 15 minutes before paclitaxel, the drug
bioavailability and maximum plasma concentration were significantly increased, moreso when
paclitaxel was given orally than IV (PO in rat study). No CNS toxicity or other side effects were
observed. Paclitaxel is a substrate of Pgp and CYP3A, suggesting that one or both of these is
inhibited by southern schisandra.2827
SOY p. 287
Glycine max beans
Ia. + 2) A black soybean extract high in hull polyphenols given for 2 months to 7 patients with
diabetes type 2 and postprandial hyperlipidemia who were concurrently taking the
antihyperlipidemic drug fenofibrate resulted in significant reductions in serum triglyceride levels
68
and LDL-cholesterol concentrations, compared to 11 patients using fenofibrate alone (PO in
human clinical study). A group of 18 patients using the soybean extract alone showed no
improvement on lipid levels.3510
Ib. + 1) In 8 children of ages 6-13 years receiving chemotherapy for cancers [including
neuroblastoma, Wilms tumor, mesenchymal tumor, adrenocrotical tumor with lung metastasis,
and glioma] with combinations of adriamycin, carboplatin, cisplatin, cyclophosphamide,
dacarbazine, etoposide, ifosfamide, irinotecan, paclitaxel, procarbazine, temozolamide, and
vincristine, in the first cycle they received no soy isoflavones, while in subsequent cycles the
chemotherapy was the same except a soy isoflavone extract tablet with 8 mg of genistein was
given daily (PO in human case series). In all, 9 cycles were given without soy isoflavones, and in
6 children 57 chemotherapy cycles with the genistein occurred over a period of 12-19 months.
During the genistein cycles there was shorter duration of neutropenia and antibiotic use and less
oral mucositis.2813
ST. JOHN’S WORT p. 289

Hypericum perforatum herb, tops
Contraindications
I. 1) This herb should not be used during pregnancy.3
HOWEVER, 38 women using S. John's wort during pregnancy were compared to 90,128 who
were not, and no association was found with its use in regard to gestational age, preterm births,
and Apgar score. There was a greater percentage of malformations in the St. John's wort group
[8.1%], but it was not statistically significant and the 3 casees did not follow a specific pattern. 3530
3) Do not take prior to surgery.1309,1890
Note CORRECTIONS: in the last line of the first paragraph, it should read: [See drug
interactions Ib.2 below.], not 'I.10'.
In the third paragraph, the brackets should read: [See drug interactions Ia.4 and Ia.7&8,
respectively.], not 'I.6 and I.8 below'.
Drug Interactions
Ia. 5) In females taking the oral contraceptives ethinylestradiol and desogestrel with St. John’s
wort extract, intracyclic bleeding increased and 3-ketodesogestrel was reduced (PO in human
study).1505
A 36-year-old woman taking a contraceptive with combined ethinylestradiol and
dienogesterol for a year began self-medicating with a St. John's wort extract at 1700 mg daily for
about 3 months when she became pregnant (PO in human case report). Four other cases of St.
John's wort association with ineffective contraception had been reported in Germany prior to that
time.3013
10) [Note CORRECTION: See Ib. 7) on p. 302 for proper category for nevirapine case series.]
16) St. John’s wort together with CYP 3A4 substrate irinotecan reduced plasma levels of SN-38
by 42% (PO in human clinical study).1342
Since irinotecan is a substrate for P-glycoprotein (in vitro),3279 inducing Pgp with St. John's
wort likely contributes to increased irinotecan efflux and reduced bioavailability.
+ 25) When 600 mg of St. John's wort extract with 4% hyperforin was given for 14 days to 12
healthy men, the bioavailability, maximum plasma concentration, and half-life of a single 5 mg
dose of finasteride were significantly reduced, compared to dosing with the drug prior to giving
the extract (PO in human study).3133
+ 26) In an open crossover study with 20 healthy male subjects, they each received 1 gram of
metformin twice each day for a week, either with or without 240-294 mg St. John's wort extract
capsules twice daily for 21 days preceeding and concurrently with the metformin (PO in human
study). Comparing pharmacokinetics of metformin alone and with the extract showed no
differences except a decrease in metformin renal clearance with the extract. In a glucose tolerance
test for both periods in 17 subjects, the area under time-concentration curve [AUC] for glucose
69
was significantly less with the extract. Insulin sensitivity was not affected, but the acute insulin
response was significantly increased by the extract.3438
Ib. + 11) A 41-year-old woman with schizophrenia was treated for 6 months with 500 mg clozapine
daily and maintained a stable 12-hour trough concentration of 0.46-0.57 mg/l, until she began
self-medicating with 900 mg daily of St. John's wort containing 27 mg hyperforin (PO in human
case report). Her mental condition deteriorated as her plasma clozapine concentration was
reduced to 0.19 mg/l and 3 weeks later to 0.16 mg/l. After discontinuing the St. John's wort for 1
month, her plasma clozapine was elevated to 0.32 mg/l and in another month to 0.41 mg/l. Her
psychiatric condition improved as well.3524
Ia. + 1) Of 100 migraine headache patients receiving 200 mg sodium valproate twice daily, half
were given added placebo and have were given 160 mg of St. John's wort extract 3 times daily for
45 days (PO in human clinical trial). Those receving the extract had significant reductions in the
intensity of their migraines and a greater decline in their frequency than those receving placebo.
The use of indomethacin as a rescue drug was not significantly different between groups.3248
IIa. 2) A freeze-dried decoction of the herb was mixed with saline and at doses of 4 ml/kg and 6
ml/kg was shown to be as or more effective, respectively, than 0.2 mg/kg IP clonidine in reducing
the withdrawal syndrome from morphine (PO in rats).3462
STINGING NETTLE p. 306

Urtica dioica leaf [not the root]
Contraindications
I. 1) Excessive internal use should be avoided in pregnancy,2,3
especially in early pregnancy, due to its emmenagogue effect when prepared as a decoction of the
plant (empirical).3087 Uterine stimulant activity has been shown with its constituent serotonin (in
vitro).3088
II. 2) Avoid use in brittle diabetes (speculative).893,2250
Use of nettle leaf extracts have shown hypoglycemic effects as well as reduced fasting insulin
resistance index with 100-200 mg of hydroalcoholic extract (IP in rats).3352 A nettle cyclical
peptide fraction designated UD-1 enhances glucose uptake by forming unique pores in skeletal
muscle cell membranes that are glucose-permeable (in vitro).2998
Ia. 1) Stewed leaf enhanced the effect of diclofenac when given to 19 acute arthritis patients (PO
in human clinical trial).386
Randomized to placebo or a commercial combination of stinging nettle with fish oil, zinc, and
vitamin E taken in capsules, 1 in the morning and 2 at night, and taking their usual regular
NSAIDs and/or analgesics, 81 patients with osteoarthritis of the knee or hip were studied for 3
months (PO in human clinical study). Compared to placebo, the defined daily doses of NSAIDs
including diclofenac, celecoxib, ibuprofen, ketoprofen, naproxen, piroxicam, sulindac, and
tenoxicam and weekly analgesic equivalents to 500 mg tablets of acetaminophen [paracetemol]
with or without opiates and aspirin were both significantly reduced in the nettle group, while the
mean scores for pain, stiffness, and function were also significantly improved.2722
Urtica dioica root
IIa. 1) A hydroalcoholic root extract at 10 mg/kg daily in animals exposed to nicotine for 28 days
significantly increased the sperm motility, count, and normal morphology, seminiferous tubule
diameter, and testosterone levels compare to nicotine-only controls (IP in mice). At 20 mg/kg
daily of root extract with nicotine, the testis weight was also significantly increased in
comparision to nicotine controls. Nicotine alone significantly reduced testosterone and sperm
70
count, motility, and normal morphology, seminiferous tubule diameter, and testis weight
compared to no-nicotine controls.3456
SWEET ANNIE p. 307

Artemisia annua herb
IIb. + 1) An artemisinin combination with curcumin is additive in killing Plasmodium falciparum (in
vitro). In addition, the semisynthetic derivative -arteether given one day after injection of
Plasmodium berghei to simulate an animal version of malaria and followed for 3 days by oral
curcumin at 100 mg/kg dosage prevented recrudescence with 100% survival in contrast to 100%
fatality 5-8 days after arteether monotherapy (IM in mice). 2914
SWEET CHERRY NEW

^ Prunus avium fruit
(cherry)
Ia. 1) In 633 patients with gout, the consumption of cherries or cherry extract for a 2-day period
reduced the risk of an acute attack in those 285 taking allopurinol by 75%, compared to a 53%
reduction in risk when using allopurinol alone (PO in human study). The preventive effect of
combining cherry products with colchicine enhanced the reduced risk from 39% for colchicine
alone to 48% with the combination. Cherry consumption independently reduced the acute attack
risk by 35% overall, with 25% less risk after a single serving increasing to 43% reduction with
once daily consumption for 2 days prior and up to 54% when 3 servings were taken in the 2 days
prior to attack. The effect of the extract intake similarly reducing the risk by 45% overall. 3299
Bing sweet cherries given after an overnight fast to 10 healthy women in 2 servings totaling
280 g significantly reduced plasma urate levels, compared to baseline (PO in human study). The
urinary urate levels were significantly increased after the cherries, compared to baseline, while
plasma C-reactive protein was somewhat reduced, indicative of some inflammatory pathway
inhibition.3329
Anthocyanin pigments from both sweet cherries and tart cherries (Prunus cerasus) at a
concentration of 125 mcg/ml were shown to inhibit COX-1 by 26% to 29% and COX-2 by 37%
to 47%, respectively, likely due to the cyanidin moiety (in vitro). The anthocyanins with fewer
sugar moieties had the greater antioxidant and COX-inhibiting activities.3301
TART CHERRY NEW

^ Prunus cerasus fruit
(sour cherry)
Ia. 1) The consumption by 24 patients with gout of 2 tablespoons cherry juice concentrate daily for
4 months or more led to a remission in acute attacks of gout in 50%, including a significant 62%
of 13 patients who had been receiving allopurinol (PO in human clinical study). The average
number of flares per year for all 24 patients was reduced from 6.85 to 2.00. The reduction in gout
attacks was significant in the total patient group and or patients receiving urate-lowering therapy,
even though the average serum urate level of those who were flare-free was still 7.8 mg/dl, higher
than the the 6.8 mg/dl saturation point of uric acid. In a related 4-month trial with 14 gout
patients, all 5 patients who were taking the NSAIDs celecoxib or indomethacin discontinued the
drugs within 60 days of starting the same dose of cherry juice concentrate, though none of the 3
using allopurinol changed their dosage (PO in human clinical study). The number of flares were
reduced in 6 of the 9 patients, compared to the rate prior to the study.3298 The concentrate used in
these studies was later revealed to be from tart cherries.3302
71
The use of 5 ml/kg of tart cherry juice for 2 weeks significantly reduced hyperuricemia by
inhibiting hepatic xanthine oxidase/dehydrogenase activity (PO in rats). It also significantly
reduced the oxidative marker MDA and increased antioxidant capacity. Though the reduction of
serum uric acid was not as great as 5 mg/kg of the positive control allopurinol, the drug provided
no antioxidant protection.3300 Anthocyanin pigments from both tart cherries and sweet cherries
(Prunus avium) at a concentration of 125 mcg/ml were shown to inhibit COX-1 by 26% to 29%
and COX-2 by 37% to 47%, respectively, likely due to the cyanidin moiety (in vitro). The
anthocyanins with fewer sugar moieties had the greater antioxidant and COX-inhibiting
activities.3301
IIa. 1) The combination of a tart cherry anthocyanin-rich extract with a suboptimal dose of the
NSAID drug sulindac used for cancer chemoprevention was shown after 19 weeks to have
fewer tumors, a smaller total tumor burden in the small intestine, and less body weight loss of
>10% than those fed sulindac alone (PO in mice). The combination was more effective in colon
cancer protection than the drug by itself.2432
IIb. 1) With exposure of adipose stem cells to lipopolysaccharide to induce interleukin-6 (IL-6), an
cytokine associated with the inflammation processes of chronic diseases such as cardiovascular
disease, the combination of 50 mcmol/L atorvastatin with 50 mcl/ml tart cherry extract or 250
mcg/ml freeze-dried cherry anthocyanins significantly reduced IL-6 secretion compared to
atorvastatin alone (in vitro). The isolated anthocynanin cyanidin-3-O-glucoside at 250 mcg/ml
had an effect equivalent to both of these combination (in vitro).3145
TEA p. 309
Camellia sinensis = Thea sinensis leaves
Contraindications
I. 2) Avoid concentrated aqueous-ethanolic extract of green tea for weight loss associated with 13
cases of hepatitis, after use from 9 days to 5 months (PO in human case reports).1508,1579,1580,2328,2577
Giving a green tea extract of concentrated catechins [63-65% EGCG, 3-4% EGC, 6-8% ECG, 8-
12% epicatechin] in doses of 0, 200, 500, or 800-1000 mg/kg/day to animals that were fasting led
to extensive organ morbidity and mortality [0/8, 3/8, 5/8, and 8/8 deaths per dose group,
respectively] within 6.5 months with most death before 13 weeks (PO in dogs). In a 13-week
follow up trial using 200 mg/kg/day, no deaths occurred and toxicity in fasted dogs was less
severe and included GI irritation, but the same dose given to non-fasted dogs resulted in much
less severe reactions. Plasma catechin levels were 2-4 times greater after fasting than after
feeding, similar to results shown with humans in a prior study.2742 Similarly, a dose of 2000
mg/kg/day of EGCG was shown to be lethal (PO in rats), but doses up to 500 mg/kg/day were not
toxic (PO in rats and PO in divided doses to pre-fed dogs), though in fasted animals a single-dose
of this amount caused morbidity (PO in dogs).2743 This suggests that use of high doses of
concentrated green tea catechins high in EGCG while fasting increases the risk of toxicity.
HOWEVER, the animal bolus dose model used with fasting dogs is considered unrealistic
when compared to human tea consumption patterns.2743 The peak plasma concentration levels in
dogs with no observed adverse effect were 4-10 times the plasma levels achieved in humans who
consumed catechins equivalent to about 10-16 cups of tea (PO in dogs and humans).2744
Drug Interactions
I. + 17) Use of a green tea catechin extract supplying 800 mg EGCG daily for 4 weeks by 42 healthy
subjects led to a 20% increase in bioavailability of the CYP 3A4 substrate buspirone (PO in
human study).2810
HOWEVER, this inhbition of CYP 3A4 was not deemed clinically significant.2810 A green tea
decaffeinated extract providing 844 mg mixed catechins daily for 14 days did not affect
alprazolam metabolism in 11 healthy subjects (PO in human study).1710
+ 18) A randomized, crossover study of consumption of 700 ml green tea or water daily for 14
days by 10 healthy volunteers, followed by a single oral dose of the antihypertensive beta-blocker
72
drug nadolol, led to significant decreases in plasma maximum concentration and bioavailability
(PO in human study). In addition, the systolic blood pressure effect of nadolol was significantly
reduced by the green tea. Nadolol was shown to be a substrate of organic ion-transporting
polypeptide [OATP]1A2 (in vitro), so based on the pharmacokinetics it is likely that green tea
inhibits OATP1A2 in the intestines.3388
In a single-dose animal study, 400 mg/kg green tea extract or 150 mg/kg epigallocatechin
gallate [EGCG] were compared with oral saline in the effects on 10 mg/kg oral nadolol when
taking them 30 minutes beforehand (PO in rat study). The extract reduced nadolol maximum
concentration and bioavailability by 85% and 74%, respectively; EGCG also significantly
reduced these 2 parameters. Urinary excretion of nadolol was decreased with the extract and
EGCG pretreatments, though its terminal half-life was unaffected, suggesting that intestinal
absorption by uptake transporters may have been inhibited.3531
III. + 5) The green tea catechin epigallocatechin gallate [EGCG] was shown to reduct the transport of
folic acid by the proton-couled folate transporter [PCFT] in Caco-2 cells and human PCFT-
expressing HEK293 cells (in vitro). EGCG competitively inhibited folic acid uptake . The drug
methotrexate is also a PCFT substrate, and its uptake was likewise competitively inhibited by
EGCG. This suggested that if folic acid or methotrexate is ingested with green tea, it may result
in reduced efficacy.3532
Ia. 3) Black tea for seven days prior to aspirin, indomethacin and reserpine reduced the incidence
of stomach ulcers, probably by altering prostaglandin metabolism and in the case of
indomethacin reducing peptic activity (PO in rats).492
Indomethacin-induced ulcers also were healed significantly better with black tea aqueous extract
at 40 mg/kg or theaflavins at 1 mg/kg after 3 days by 74-76% (PO in mice). Stomach acid
secretion was not modulated, but gastric COX-1 and -2 and PGE were increased.2752
IIa. 1) Black tea for 7 days reduced stomach ulcers produced by ethanol (alcohol) (PO in rats).492
Furthermore, hepatotoxicity induced by a diet with 15% ethanol by volume for 30 days was
reduced when co-administered with 10 ml/kg 2.5% aqueous extract of black tea (PO in rats). This
was shown by significant reductions in serum AST, ALT, and GGT and in malondialdehyde and
increases in SOD and catalase activities compared to ethanol alone, presumably by decreasing
oxidative stress.3151 In addition, after 28 days of intoxication with ethanol the reduction of
enzymatic and non-enzymatic antioxidants in the liver, serum, and brain were considerably
prevented by consumption of black tea for 1 week prior and concurrently (PO in rats).3150
4) Green tea extract increased apoptosis in ER+ MCF-7 breast cancer cells when combined with
tamoxifen compared to tamoxifen alone and decreased MCF-7 graft tumor size and suppressed
angiogenesis more than either agent alone (PO in mice).2039
In ER+ MCF-7 cells epigallocatechin gallate [EGCG] inhibits growth, decreases Skp2, and
increases p27-Kip1 in a dose- and time-dependent fashion; both tamoxifen synergistically
enhance EGCG inhibition of MCF-7 cells and further down-regulate Skp2 (in vitro).3468
In mice implanted with ER-negative [ER-] MDA-MV-231 human breast cancer cells, when
given 75 g/kg tamoxifen, 25 mg/kg EGCG, or the combination, only the combination
significantly reduced tumor growth, 80% less compared to controls (IP in mice). This was likely
due to the concomitant 85% reduction in epidermal growth factor receptor and 78% decrease in
mammalian target of rapamycin, compared to controls.3467 In ER- MDA-MV-231 breast cancer
cells, cell growth was significantly and synergistically inhibited by the combination of EGCG at
25 M and tamoxifen at 1 M after 7 days, compared to either individual treatment (in vitro).3469
+ 6) The component catechin given in 2 daily doses of 150 mg/kg with ciprofloxacin to mice with
chronic bacterial prostatitis significantly reduced the E. coli in the prostate compared with use
of ciprofloxacin alone (PO in rats).3038
73
+ 7) Theanine at 4 and 8 mg/kg was shown to significantly attenuate opioid withdrawal symptoms
after 90-150 minutes and 30-150 minutes, respectively, when given after morphine dependence
was established (SC in monkeys). The withdrawal signs reduced by theanine included fighting,
pacing, retching, shaking, rigid abdominal muscles, and masturbation.3397
IIb. + 3) In ER+ MCF-7 human breast cancer cells epigallocatechin gallate [EGCG] inhibits growth,
decreases Skp2, and increases p27-Kip1 in a dose- and time-dependent fashion; paclitaxel
synergistically enhances EGCG inhibition of MCF-7 cells and further down-regulate Skp2 (in
vitro).3468
When 25 M EGCG was combined with 5 M raloxifene, ER-negative [ER-] MDA-MV-231
human breast cancer cells were significantly reduced by 96% after 7 days, compared to contols
(in vitro). After 48 hours the reduction in cell numbers by the combination was significantly
greater than from exposure to either agent alone, along with 21.2% and a 31.5% reductions in the
phosphorylation of epidermal growth factor receptor and protein kinase B, respectively, after only
18 hours.3470
TEA TREE p. 317

Melaleuca alternifolia leaf oil
Ia. 1) In a placebo-controlled trial a microemulsion formulation of tea tree oil, diclofenac, and
minoxidil used by 11 men was compared with minoxidil alone for 11 men and placebo for 10
men, applied twice daily for 32 weeks for the treament of androgenic alopecia (TP in human
clinical study). Based on average hair count, weight, and thickness and patient self-assessment,
the combination was significantly better than placebo and minoxidil alone.3371
THUNDER GOD VINE p. 318

*Tripterygium wilfordii peeled root
Ia. 1) An extract given to 10 rheumatoid arthritis patients using NSAIDs, 8 also taking
prednisone, found 8 of 9 had improved clinical and laboratory findings at doses over 360 mg
(PO in human clinical study).1417
External use in a 6-week randomized, placebo-controlled, double-blind trial involved 31
applying the tincture 5-6 times daily and 30 using placebo (TP in human clinical study).
Concurrent methotrexate, NSAID, and auranofin stable doses were allowed. Response rate with
the tincture was 58% versus 20% with the placebo. Compared to placebo, significant
improvements were found with tincture clinically for tender joint and swollen joint counts, grip
stength, and morning stiffness, along with laboratory measurements of erythrocyte sedimentation
rate [ESR], C-reactive protein [CRP], and rheumatiod factor [RF] levels, as well as patient and
physician global assessments.3281
In a trial of 146 rheumatoid arthritis patients given 40-60 mg/day chloroform/methanol extract
plus methotrexate for 12 months, 39 had used disease-modifying anti-rheumatic drugs prior; 23
had been on methotrexate alone, while 19 used a combination including methotrexate (PO in
human clinical study). Significant reductions were found clinically with tender joint and swollen
joint counts, and morning stiffness, and in laboratory measures of ESR and CRP after 3 months
and 12 months. During the study, 10 withdrew due to adverse events, but most adverse effects
were mild. Menstrual irregularity occurred in 16 of the 22 premenopausal women in the study.3280
The unique diterpene triepoxide component triptolide inhibits T-cell transcriptional activation
of NF-B and IL-2 (in vitro).2861 Triptolide has been shown to bind to human transcription factor
TFIIH subunit XPB, inhibiting DNA-dependent ATPase activity and RNA polymerase II-
mediated transcription (in vitro).2862
Ib. 1) The dry extract was used at 60 mg daily for 6 weeks in 12 patients with ankylosing
spondylitis, 8 of whom were also using methotrexate, sulfasalazine, or a combination of both
74
(PO in human case series). Compared to baseline assessments, after 3 and 6 weeks there were
significant improvements in disease activity and functional index scores, global score, and
physician assessments. No liver enzyme or blood count changes were found.3282
TIBETAN RHODIOLA NEW

^ Rhodiola crenulata root
(Chin.: hong jing tian)
Ia. 1) In a randomized, placebo-controlled, double-blind study with 57 patients with moderate to
severe chronic obstructive pulmonary disease [COPD], 38 were given a 250 mg Tibetan rhodiola
root capsule twice daily for 12 weeks, while 19 received placebo, in addition to their standard
treatment(s) (PO in human clinical trial). Of those receiving the root, 23% were taking xanthines,
17% used long-acting muscarinic antagonists [LAMA], 22% took long-acting beta-2 agonists
[LABA] with inhaled corticosteroids, while 12% used the LABA plus corticosteroids together
with LAMA. Additionally, 6% used LABA alone, 11% used a combination of short-acting MA
and BA [SAMA+SABA], and 9% took antihistamines. Those taking the root capsules had
significant improvements in forced expired volume in 1 second [FEV1] and workload compared
to baseline, and significantly improved tidal volume and ventilatioin-CO2 output ration at peak
exercise compared to placebo. The tiadal breathing and ventilation efficiency were also
significantly improved with taking the root.
TULSI NEW
^ Ocimum tenuiflorum = Ocimum sanctum leaves
(holy basil, sacred basil; Sans.: tulasi)
Drug Interactions
Ia. 1) When powdered leaf was given in 1 gram doses each morning for 30 days to 17 diabetes type
2 patients taking chloropropamide, glibenclamide, glipizide, or penformin and fasting blood
sugar and glycated serum proteins were compared to baseline, a significant 20.8% reduction in
blood glucose and 11.2% decrease in glycated proteins was found (PO in human clinical study).
In addition, total cholesterol, LDL-cholesterol, and VLDL-cholesterol were also significantly
decreased. By way of further comparison, the blood sugar and lipid values in 10 diabetic control
patients were slightly increased in 1 month.3308
When 30 male type 2 diabetics were given 2 grams of powdered leaf daily for 3 months,
significant reductions were found in the numbers of those with polydypsia, polyphagia, and
headaches, as well as lower blood pressures (PO in human clinical study). These effects were all
greater when the same dose of equal parts tulsi and neem (Azadirachta indica) powders were
given to 30 other type 2 diabetic patients.3309 The leaf ethanolic extract has been shown to
increase the secretion of insulin from perfused pancreas, isolated islet cells and a clonal beta-cell
line taken from rats (in vitro),3310 while the aqueous, methanolic, and chloroform extracts all
inhibited pancreatic and small intestinal glucosidases from mice, similar to acarbose (in vitro).
The chloroform extract also inhibited alpha-amylase (in vitro).3311
II. 1) When 20 mg of ethanolic extract derived from 100 mg of leaf was given twice daily for 5 days
prior to an injection of pentobarbital, the sleeping time was significantly prolonged (PO in
mice).3220
IIa. 1) After peripheral neuropathic pain was induced by injection of vincristine sulfate for 10 days,
100 or 200 mg/kg of tulsi methanolic extract or its saponin fracton were given for 14 days (PO in
rats). Both the extract and fraction at both doses significantly reduced the vincristine-induced pain
associated with hind paw pin pricks, paw cold from acetone, and paw heat from hot plate,
compared to the effects of no treatement, beginning on day 2 for the pin pricks and acetone cold
effects and day 6 for the heat. The fraction was significantly more effective when compared to the
75
extract for these measures over the same time periods, and 200 mg was significantly better than
100 mg of the fraction for all 3 measures after 6 days, as was pain from tail immersion in cold
water. The same pattern of significant comparative results were found with the reduction of
markers of oxidative stress.3179
2) When the tulsi ethanolic extract was given at 200 mg/kg body weight after hepatotoxicity had
been induced by acetaminophen, improvements in albumin globlulin ratio and serum alkaline
phosphatase and transaminases AST and ALT were significantly better with the extract (PO in
rats). Also, the histopathologic damage to the liver was less and signs of regeneration were
greater than with no treatment.3181
3) An aqueous extract of tulsi given at 200 mg/kg body weight prevented diarrhea, stomach
ulceration, and intestinal damage caused by 2.4 mg/kg of the NSAID drug meloxicam (PO in
rats). The same dose of extract also helped alleviate hepatotoxicity and maintain hemoglobin
levels after 1.2 mg/kg meloxicam, but did not protect the kidney or heart at the higher NSAID
dose.3183
4) Doses of a tulsi hydroalcoholic extract given at 50 or 75 mg/kg for 30 days helped protect
against heart damage induced by 2 doses in 2 days of subcutaneous [SC] isoproterenol at 85
mg/kg (PO in rats). The extract significantly increased cardiac levels of antioxidant enzymes
superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as
reducing the lipid peroxidation marker malondialdehyde in the heart and cardiac damage markers
AST, LDH, and CPK in the serum.3185 With 50 mg/kg fresh tulsi leaf homogenate daily for 30
days, heart damage from a single dose of 85 mg/kg SC isoproterenol was prevented (PO in rats).
After tulsi only, the amount of superoxide dismutase [SOD] and catalase increased significantly
in the heart. Without the tulsi, the isoproterenol significantly decreased heart SOD and
glutathione peroxidase and produced evidence of cardiac necrosis. After tulsi and isoproterenol,
only slight myocardial damage was detected.3239
5) The salivary gland damage caused by high-dose radioiodine [131 I] was reduced when the
tulsi aqueous extract was given for 5 or 15 days prior at 40 mg/kg (PO in mice).3184,3186 The
extract prevented the increase in lipid peroxidation in the salivary glands and kidneys after 24
hours, compared to those treated with 131 I, and lessened the depletion of reduced glutathione in
the liver.3186 Parotid gland atrophy and lipomatosis from 131 I was shown after 3 months when
exposed once or after 6 months with 2 exposures [3 months apart], while those receiving the tulsi
extract before the radioiodine had salivary tissue similar to controls.3184
6) The hepatotoxicity and immunosuppressant effects of the antituberculosis combination of
isoniazid, rifampicin and pyrazinamide were significantly reduced by powdered tulsi given at
200 mg/kg for 21 days (PO in guinea pigs). Specifically, the serum AST and alkaline phosphatase
were significantly reduced and normalized, respectively, and the phagocytic percentage and other
parameters of neutrophilic function were normalized or enhanced, compared to these parameters
of those receiving only the antituberculosis drugs.3198
7) The ethanolic extract of the leaves given at 100 mg/kg for 3 days prior to aspirin being used
to induce stomach ulcers resulted in a significant 63% reduction in ulcers, associated with a
34.6% increase in mucin secretion and a 58% reduction in total acidity and peptic activity (PO in
rats). Similarly, stomach ulcers induced by alcohol (ethanol) were reduced by 54%, significantly
better than from using 10 mg/kg omeprazole (PO in rats). When given for 20 days after a 3-day
induction of ulcers by acetic acid, the extract significantly healed ulcerations after 5 and 10 days
and completely healed them after 20 days, equivalent to omeprazole (PO in rats).3218
8) When 20 mg of ethanolic extract derived from 100 mg of leaf was given twice daily for 5
days prior to an injection of amphetamine, it significantly and completely prevented
amphetamine toxicity from resulting in death (PO in mice).3220
IIb. 1) The genotoxic chromosomal damage to human lymphocytes induced by the synthetic
progestin drug cyproterone acetate was reduced dose-dependently by a water extract of tulsi (in
76
vitro). This effect may help reduce the risk of carcinogenesis from cyproterone use in patients as
an antiandrogen for prostate cancer (speculative).3196
TURMERIC p. 324
Curcuma aromatica, Curcuma longa = Curcuma domestica root
Drug Interactions
Ia. + 1) When curcumin was given at 300 mg daily for 6 days to 12 healthy subjects, it reduced the
bioavailability, peak plasma concentration and increased total clearance of a single dose of
talinolol (PO in human study). The mechanism was unclear due to the small dose and group and
short duration.2806
Ia. + 3) In 50 patients with osteoarthritis of the knees, for 3 months along with prescription
nonsteroidal anti-inflammatory drugs (NSAIDs), half were give 200 mg curcumin mixture
formulated with phosphatidylcholine and half were given placebo (PO in human clinical study).
Those using curcumin had significant improvements in median scores for pain, stiffness, physical
function, walking ability, edema, and plasma C-reactive protein levels compared to placebo.
NSAID use was decreased by 63% in the curcumin group, significantly more than the 12%
reduction with placebo.2721 With half using the same curcuminoid mixture [75% curcumin, 15%
demethoxycurcumin, 10% bisdemethoxycurcumin] and dose as the 50-patient 3-month study, an
8-month study with 100 osteoarthritis patients using NSAIDS or acetaminophen showed
significant improvements compared to the control group in pain, stiffness, and physical functions
including walking distance and for inflammatory markers including IL-1, IL-6, soluble CD40
ligand, and ESR (PO in human clinical study). In addition, the curcumin group used significantly
less NSAIDs like celecoxib and/or acetaminophen and other drugs and nondrug treatments and
had less gastrointestinal complication, distal edema, hospital admissions, and management costs
than the control group.2802 In a 6-week randomized, placebo-controlled, double-blind study of 40
patients with knee osteoarthritis using the NSAID naproxen, 19 were given 1500 mg
curcuminoid daily (PO in human clinical study). By the end of the study, those taking
curcuminoids had significant improvements in scores for pain and physical function compared to
placebo. In addition, 84% of those taking curcuminoids were taking less naproxex, significantly
better that the 19% on placebo. The average naproxen usage with curcuminoids was 250-500 mg
daily, compared to 500-750 mg daily with placebo.3433
In addition, in patients with knee osteoarthritis taking a non-curcuminoid extract fraction with
12.6% polysaccharides, those 29 taking 1000 mg daily of the fraction for 42 days used
significantly less acetaminophen to control pain during this time than the 29 subjects who were
using placebo (PO in human clinical trial). Those taking the extract fraction also had significantly
less pain, better function, and greater improvement in orthopedic examinations than those taking
placebo. The significant improvements included a higher percentage of elimination of joint
tenderness, effusion, crepitation, and limitations of joint movement compared to placebo. Extract
adverse events involved 2 cases of mild dyspepsia.3247
A proprietary curcuminoid product with 42 mg of curcumin per capsule in a matrix to
maximize absorption was used in doses of 4-6 capsules daily for 6 months by 820 patients with
painful osteoarthritis, 54.3% using NSAIDs and 64.7% taking analgesics. After 6 months patients
were able to discontinue analgesics and NSAIDs by more than half, while also obtaining
significantly reduced pain and increased flexibility. Tolerance was excellent.3415 A comparative
study with 91 knee osteoarthritis patients randomized to receive 2 grams daily of turmeric extract
[1 gram curcumin] or 800 mg of ibuprofen for 6 weeks found the 45 given turmeric extract had
equivalent efficacy, adverse effects, and patient satisfaction as those on ibuprofen after 6 weeks
77
+ 4) Patients with chronic anterior uveitis, including 56 with autoimmune, 28 with herpetic, and 22
with other or unknown causes, suffering up to 4 relapses in the previous year were given 240 mg
daily for 12-18 months of curcumin formulated with phosphatidylcholine together with the
standard treatment they had been receiving that involved systemic steroids, immune
suppressants, antiherpetics, and antitoxoplasmic drugs or eye drops with steroids, mydriatics,
cycloplegics, and NSAIDs (PO in human clinical trial). The number of patients with relapses
after the curcumin was instituted was 19, and the number of relapses per year for the group was
36, compared to the 275 relapses per year prior to the curcumin.2803
+ 5) In 508 tuberculosis patients with treatment-induced hepatotoxicity, 192 were given isoniazid,
rifampicin, and pyrazinamide along with ethambutol for 2 months, which were continued for 4
more months without the pyrazinamide, while 316 were given the same schedule of drugs
together with 1 gm/day of turmeric extract with 25% curcumin and 1 gm/day of Tinospora
cordifolia powder enriched 50% with its 10:1 hydro-ethanolic extract (PO in human clinical
study). The extract concentrates were approximately equivalent to 6 gm/day of each herbal
powder. After the 6 months, those using the herbal extracts had significantly lower markers for
hepatotoxicity including average serum AST, ALT, and bilirubin levels, significantly less poorly
resolved liver parenchymal lesions, and better compliance than the controls. The extract group
also had significantly less TB-positive sputum after 4 weeks.2995
+ 6) When 1 gram of a lecithinized formulation of curcumin was given for 4 weeks to 25 diabetes
type 2 patients on oral hypoglycemics, significant improvements from baseline levels of foot and
ankle edema and other signs of microangiopathy were shown, along with significant
improvement in Karnofsky scale scores for general health compared to the 25 control subjects
+ 7) In 45 rheumatoid arthritis patients, groups were randomly selected to receive 500 mg
curcumin, 50 mg of diclofenac, or both for 8 weeks to monitor scores in disease activity, joint
swelling, and tenderness, along with safety outcomes (PO in human clinical study). All 3 groups
had significant improvements in these 3 disease outcomes, but the combination and cucurmin
alone showed better scores than diclfenac alone, while diclofenac had more adverse events than
the combination and curcumin alone had none.3103
+ 8) In a randomized, observer-masked study of 45 patients with major depression, curcumin at
1000 mg daily for 6 weeks with a response rate of 62.5% was equivalent to the response to 20 mg
of fluoxetine of 64.7%, but the combination was most effective at 77.8%, though the differences
were not statistically significant (PO in human clinical study). The investigators ranked responses
as good or excellent for 70.5% of those on fluoxetine, 75% on curcumin, and 83.3% on both. The
medications were well tolerated.3348
+ 9) When a lecithinized formulation of curcuminoids was given in 100 mg doses 3 times daily
with meals to cancer patients with chemotherapy AE [adverse effects] from 51% using 5-
fluoruracil for colorectal or gastric cancer, 11% using 5-fluorouracil and cisplatin for
genitourinary cancers, 6% using vinblastine and CCNU for kidney cancer, 23% using cisplatin
and gemicitabine for lung cancer, and 9% using MOPP/ABVD/COPP for hematological
malignancies, the adverse effects of nausea and vomiting, diarrhea or constipation, malnutrition
or weight loss, memory or cognitive dysfunction, infections, neutropenia, and cardiotoxicity were
all significantly reduced in the 40 patients receiving curcuminoids, compared to 40 control
patients (PO in human clinical study).3363
In addition, in a randomized, placebo-control, double-blind trial with 180 mg of lecithinized
curcuminoids daily for 8 weeks together with standard chemotherapy in 40 cancer patients with
solid tumors, mostly colorectal, gastric, and breast cancers[61.5%], the quality of life was
significantly increased along with significant decreases in markers of systemic inflammation
including TNF-a, TGFb, IL-6, substance P, hs-CRP, CGTP, and MCP-1 compared to 40 patients
with comparable cancer and chemotherapy who received placebo (PO in human clinical trial).
Chemotherapy commonly used in these patients included topotecan-cyclophosphamide-
78
etoposide or cyclophosphamide-methotrexate for breast cancer, docetaxel-cisplatin-5-
fluoruracil for gastric cancer and breast cancer, and 5-fluoruracil regimens for colorectal
cancer.3407
+ 10) A mouthwash with 0.004% curcumin, diluted 1:5 for use for 1 minute 3 times daily for 20
days, was utilized for treating oral mucositis induced by chemotherapy with carboplatin,
cisplatin, or taxol and radiotherapy in 10 cancer patients (PO in human clinical study). After 20
days the pain, ulceration, and severity of mucositis based on the WHO mucositis scale were all
significantly improved, compared to standard treatment with a 0.2% chlorhexidine diluted 1:1 for
10 cancer patients.3485
IIa. + 5) In combination with weekly IP paclitaxel, curcumin given at 100 mg/kg daily for 5 weeks
significantly inhibited MDA-MB-231 tumor cell proliferation, increased apoptosis (PO in mice,
in vitro) and inhibited breast cancer tumor size, compared to paclitaxel alone (PO in mice). This
was associated with a decrease in MMP-9 and inhibition of paclitaxel-induced NF-B
activation.3117 The addition of 2% curcumin to the diet significantly reduced the incidence of lung
metastasis with the use of paclitaxel following surgical removal of human breast cancer cell
tumors, compared to paclitaxel alone (PO in mice). While paclitaxel induces the activation of
IB kinase, NF-B, and NF-B antiapoptotic gene products involved in prolifereation and
metastasis of tumor cells, curcumin inhibited these drug-induced effects along with the activation
by paclitaxel of COX-2 mRNA and promoter activity (in vitro). Curcumin also potentiated
paclitaxel cytotoxicity to breast cancer cells (in vitro). Curcumin significantly reduced metastasis
even when used alone (PO in mice). The anti-metastatic effect of curcumin with the low
paclitaxel dosage was equivalent to a high dose of paclitaxel, suggesting the potential for an
equally effective and less toxic treatment (speculative).2781
Based on a Phase I trial with standard docetaxel dosing in 14 patients with advanced and
metastatic breast cancer, a 6-gram curcumin daily dose for 7 consecutive days every 3 weeks is
recommended (PO in human clinical study). Of 8 evaluable patients receiving a maximum of
8g/day curcumin, 5 showed a partial response and 3 had stable disease.3119 As shown by plasma
levels and a reduction in biomarkers such as PGE2, curcumin doses of 3.6 grams daily are
recommended for cancers outside of the gastrointestinal tract (PO in human clinical study),2785
though another study showed negligible distribution outside the gut after 7 days at this dose (PO
+ 6) Liposomal curcumin enhanced the effects of suboptimal concentrations of cisplatin against
xenograft head and neck sqamous cell carcinoma [HNSCC tumors], significantly better than
either agent alone (IV in mice). Curcumin inhibited IKK, leading to NFB inhibition, a different
growth signaling pathway than that of cisplatin. The combination of these 2 agents also
suppressed 2 HNSCC cell lines (in vitro).2877 [See IIb. 1) in the book.]
+ 7) Curcumin at 100 mg/kg dosage given 3 times following intramuscular injection of -
arteether, one day after injection of Plasmodium berghei to simulate an animal version of
malaria, prevented recrdescence with 100% survival in contrast to 100% fatality 5-8 days after
arteether monotherapy (PO in mice). Curcumin in combination with artemisinin are additive in
killing Plasmodium falciparum (in vitro).2914
+ 8) Curcumin at 1gm/kg daily in combination with thrice-weekly IP gemcitabine significantly
reduced bladder cancer tumor volume and microvessel density, compared to gemcitabine alone,
while also blocking activation of NF-B and inducing apoptosis (PO in mice, in vitro), and
decreasing cyclin D1, VEGF, COX-2, and proliferation marker Ki-67 in the bladder cancer tissue
(PO in mice).3118
Doses of curcuminoids [90% curcumin] of 8 g/day in treating advanced pancreatic cancer in a
Phase II trial with 17 patients were not tolerated by 5 patients and needed to be reduced to 4 g/day
in 2 others when used with IV gemcitabine given in 3 of 4 weeks until toxicity, disease
79
progression, or death occurred (PO in human clinical study). Of 11 evaluable patients, disease
stabilized in 4 and partially improved in 1.3120
+ 9) Curcumin given at 200 mg/kg 30 minutes after a dose of acetaminophen that produces
kidney toxicity resulted in normalized kidney tissue structure and significantly lower
malondialdehyde marker of oxidative damage and increased antioxidant enzyme activity
compared to those receiving only acetaminophen (IP in rats).3122
+ 10) After 9.9 g/kg/day of ethanol was given for 30 days, 80 mg/kg of curcumin was given
concurrently with the 25% alcohol to one group that then showed significantly reduction in signs
of hepatotoxicity compared to those receiving only the alcohol (PO in rats). These signs included
elevated serum AST, alkaline phosphatase, total cholesterol, phospholipids, free fatty acids, and
lipid peroxides called thiobarbiturics acid reactive substances.1832 In another study of alcoholic
liver disease, those given only ethanol for 4 weeks developed fatty liver, inflammation, and
necrosis accompanied by NF-B activation and induction of COX-2, iNOS, cytokines, and
chemokines, whereas those give 75 mg/kg/day of curcumin with the alcohol avoided these
biochemical and pathological changes by blocking the NF-B activation (PO in rats).3159
+ 11) The hepatotoxicity and immunosuppressant effects of the antituberculosis combination of
isoniazid, rifampicin and pyrazinamide were significantly reduced by powdered turmeric given
at 200 mg/kg for 21 days (PO in guinea pigs). Specifically, the serum AST and alkaline
phosphatase were significantly reduced and normalized, respectively, and the phagocytic
percentage and other parameters of neutrophilic function were normalized or enhanced, compared
to these parameters of those receiving only the antituberculosis drugs.3198
+ 12) The use of 15 mg/kg curcumin in conjunction with 10 mg/kg docetaxel to treat A549-
xenograft of non-small cell lung cancer showed a synergistic effect that was significantly better
than docetaxel alone (IV in mice). A normalization of the significantly elevated alanine
aminotransferase from docetaxel alone was achieved by its combination with curcumin,
indicating a prevention of hepatotoxcity. The same synergy was shown for enhancing cytotoxicity
against the A549 lung cancer cells (in vitro). 3319
+ 13) After receving daily 150 mg/kg curcumin for 15 days prior to lung infection with Klebsiella
pneumoniae and/or 30 mg/kg oral clarithromycin 12 hour post infection, comparisons of
outcomes of these 3 groups with controls were made (PO in mice). The clarithromycin alone
decreased bacterial load and inflammation, whereas curcumin alone had no impact on bacterial
load, but alone and combined with the antibiotic curcumin had a more significant reduction in
inflammatory parameters including neutrophil influx. The combination led to control of both
infection and inflammation, reducing lung damage more than each individually.3516
IIb. + 4) Liposomal curcumin has shown synergistic effects of growth inhibition and apoptosis in
colorectal cancer cells when combined with oxaliplatin at a 4:1 ratio, as curcumin was a better
growth inhibitor than oxaliplatin (in vitro), though there was no advantage when using oxaliplatin
with curcumin for xenographic colon tumors (IV in mice).2782
Doses of turmeric extract from 440 mg to 2.2 grams [36-180 mg curcumin] daily and even
curcumin doses of 450 mg to 1.8 grams daily have been shown to have poor oral bioavailability
systemically but is retained in the gut with good safety, serving as an advantage for application in
colorectal cancer patients refractory to chemotherapy (PO in human trial).2488,2785 In 5 of 15
patients receiving the extract this disease remained radiologically stable for the 2-4 months of
treatment.2488 Of those 15 patients receiving the curcumin one became nauseous with 450 mg and
another had diarrhea with 900 mg.2785 Curcumin has been found in colon mucosa in levels
sufficient to explain its pharmacological activities (PO in rats),2783 including in malignant
colorectal tissue after 3.6 grams of curcumin have been taken daily for 7 days (PO in human
clinical study).2786 Evidence (in vitro and PO in human clinical trials) suggests curcumin may be
useful in colon cancer chemoprevention (speculative).2784
80
VALERIAN p. 328
*Valeriana officinalis root/rhizome
1a. 1) A combination of 3 herbal hydroethanolic extracts including valerian root 3-6:1, hops
(Humulus lupulus) strobiles 4-8:1, and passion flower (Passiflora incarnata) herb 4-7:1 was
found to markedly improve symptoms associated with benzodiazepine withdrawal phase in 107
patients of an average age of 54 years (PO in human clinical study). The extracts were begun with
1-2 tablets daily as benzodiazepine dosage was reduced for 2 weeks, and continued for the next 4
weeks after benzodiazepine use was stopped. Improvement was shown for pronounced tiredness
in 76% and general unrest in 71%, according to subjective assessment of patients. Sleep improved
in 68% by the end of the treatment, and 74% had more motivation and drive than at the
beginning. At the end, 62% were calmer and better able to cope. No adverse drug events occurred
in any patients.2634
WILD YAM p. 334

Dioscorea villosa root
Contraindications
I. 2) Avoid use in liver disease such as viral hepatitis, toxic hepatitis, or cirrhosis (empirical).777
Use of 0.8 gm/day of a 50:1 extract for 28 days led to some inflammatory and fibrotic changes in
the liver (PO in rats).2979
II. 3) Avoid long-term use by those with kidney dysfunction or taking drugs that alter kidney
function (speculative), since use of 0.8 gm/day of a 50:1 extract for 28 days led to fibrotic
changes in the kidney (PO in rats).2979
YOHIMBE p. 340
*Pausinystalia yohimbe = Corynanthe yohimbe bark
Contraindications
I. 1) Do not use in schizophrenia,76,184 since psychotic episodes can be induced by its alkaloidal
constituent yohimbine (IV in human clinical study).76
Of the 238 adverse events reported to the California Poison Control System from 2000-2006 in
association with yohimbine-containing products, 5% involved altered mental status or behavior
(empirical).2766
3) Avoid use during anxiety,344 due to its exacerbation by the alkaloidal component yohimbine
(PO and IV in human clinical studies).76,79,344
association with yohimbine-containing products, 33% involved anxiety or agitation
(empirical).2766
4) Do not use in high blood pressure,344 due to its exacerbation by 0.2 mg/kg yohimbine in 9
hypertensive patients, 10 mg in 29 hypertensives, or 21.6 mg in 25 hypertensives (PO in human
clinical studies).534,535,536
association with yohimbine-containing products, 25% involved hypertension (empirical).2766
8) The conditions of angina pectoris and other heart disease produce greater risk with
yohimbine (PO in human studies).344
association with yohimbine-containing products, 43% included tachycardia and 12% involved
chest pain (empirical).2766
81
APPENDICES
Appendix A p. 345
HERBALS TO BE USED WITH CAUTION
A.2 Due to Potential Photosensitizing Effect
A.2.2 Other plants not in the carrot family can also act as photosensitizers. Oftentimes the
utilized parts and photoactive components these plants, including citrus peels and their essential
oils, are most sensitizing following topical exposure.
Ingestion of citrus, on a daily basis has been associated with a significantly increased risk
of malignant melanoma of the skin, independent of age and other dietary and lifestyle factors. In
particular, half of a grapefruit once or more per week or a 6-ounce glass of orange juice 5-6
times or more per week (but not 6 oz. grapefruit juice or an orange consumed with the same
frequency, respectively) significantly increased the hazard ratio for melanoma. This is based on
analysis of 63,810 women (Nurses' Health Study 1984 to 2010) and 41,622 men (Health
Professionals Follow-Up Study, 1986 to 2010), most of whom are Caucasian. Such "positive
association seemed to be more apparent" in those with susceptibility to sunburn as children, more
blistering sunburns, more time in direct sunlight, and residences with higher annual flux in
ultraviolent light, due in part to significant associations between consumption of grapefruit with
melanomas only on body areas with continual higher sun exposure.3506
A.2.2 Rutaceae – Rue Family
Grapefruit fruit or peel (Citrus paradisi)
Orange fruit juice (Citrus sinensis)
A.8 Bioactivations of Phytochemical Procarcinogens and Potential Toxins ^

Metabolism of phytochemicals can sometimes lead to the bioactivation of metabolites
into toxins or carcinogens. This typically occurs in the liver and often involves Phase I
cytochrome P450 (CYP) isozymes or less frequently Phase II conjugating enzymes, especially
sulfotransferases. In both cases, with continual exposure to significant doses the end-products of
metabolism show enhanced organ toxicities, compared to exposure to the native compounds
found in the plant itself. Conversions by intestinal bacteria also have the potential to produce
new toxins, as does the exogenous conversion, e.g., transformation of coumarin by molds or
fungus to anticoagulant 4-hydroxycoumarins. (See Appendix B.5.1.) Production in some foods
such as peanut and corn products of liver carcinogenic aflatoxins by Aspergillus flavus or other
Aspergillus species of fungus is another cause of concern. However, only those toxic activations
that result primarily as a consequence of human metabolism will be considered here.
A number of herbs and extracts should not be taken internally unless appropriately
processed to remove the potentially toxic or carcinogenic compounds, such as those containing
aristolochic acids or pyrrolizidine alkaloids. For some phytochemicals, such as teucrin A, one of
the furano neoclerodane diterpenoids in Teucrium spp., the toxicity can be increased in the
presence of an appropriate CYP inducer (in this case, one like St. John's wort containing
hyperforin). In contrast, its toxicity could theoretically be diminished when exposed to the
isozyme-specific CYP 3A4 inhibitor (such as a CYP 3A4 inhibitor like grapefruit juice to help
diminish toxicity from exposure to teucrin A). Reducing toxin activation by this approach is
intriguing and would be most effective if a single isozyme or metabolic pathway has been
identified and can be manipulated. However, in vivo research is necessary to confirm this
potential. In regard to procarcinogens, the use of certain herbal inhibitors of CYPs may function
82
as an important type of chemoprevention. On the other hand, it is important to avoid combining
herbs that could induce enzymes involved in activating potential toxins or procarcinogens with
herbs or other sources of these compounds. (See Appendix B.7.)
Major references: 150, 2792
A.8.1 Bioactivations by Cytochrome P450 Isozymes (CYPs) and Sulfotransferases (STs) ^

Phytochemicals Common Herb Sources Activators Metabolite Toxic
Effects
aristolochic Aristolochia *(Aristolochia spp.) herbs2817 CYPs 1A1/2;2816 kidney
150,1357,2818
carcinogens,
acids Wild ginger *(Asarum canadensis) rhizome150 ST 1A2792 kidney
150,1357
toxins
estragole Basil (Ocimum basilicum) herb150,400 CYPs 1A2,2A6, liver carcinogen,150,759,760
150,400
Fennel (Foeniculum vulgare) seeds 2C19,2D6,2E1; mutagenic2820
150,400 2792
Tarragon (Artemisia dracunculus) leaf STs
400
methyl- Asarabacca (Asarum europeum) rhizome CYPs 1A2,2C9, liver carcinogen759,760
400 2792
eugenol Wild ginger *(Asarum canadensis) rhizome 2C19, 2D6; STs
pulegone Am. pennyroyal *(Hedeoma pulegoides)150,2792 CYPs643 1A2, liver
642,644,645
toxin
Eur. pennyroyal *(Mentha pulegium)150,2792 2C19,2E12821
pyrrolizidine Borage herb *(Borago officinalis),150 CYPs 2B6,2792 liver
38,144,236,333,590
toxins
alkaloids Comfrey plant *(Symphytum officinale),150,2792 3A41183
2792
Common groundsel herb *(Senecio vulgaris),
Gravel root *(Eupatorium purpureum),150
Rattlebox herb *(Crotalaria spp.),2792
Tansy ragwort herb *(Senecio jabocaea)2792
safrole Sassafras *(Sassafras albidum) root bark150 CYPs2819 2A6, liver
150,759,760,2819
carcinogen,
2C9,2D6,2E1; mutagenic2820
2792
STs
teucrin A Germander (Teuchrium chamaedrys)2822 CYP 3A42792 liver
1516,1517,1518
toxin
83
Appendix B
HERBAL-DRUG INTERACTIONS
[Note CORRECTIONS: In Appendices B and E in the first l00 copies of the book, asterisks (*) are
missing in front of the scientific Latin names for a number of listed herbs designated with * in the
main body of the text as containing potentially toxic compounds. (For example, European
pennyroyal herb *(Mentha pulegium) near the top of page 366 lacks an asterisk in these books.)
In Appendix B the other herbs that may be missing the * include: Aloes, Black cohosh, Cayenne,
Celandine, Chaparral, Chinese rhubarb, Cinchona, Coffee, Cubeb, Garlic, Juniper, Kava,
Licorice, Madagascar periwinkle, Sage, Sassafras, Thuja, and Valerian.]
B.1 Modifying Intestinal Absorption of Medicines and Phase III Metabolism

p. 361
B.1.1.b.i & B.1.1.b.ii Even black tea with its known high tannin content and astringency does
not completely block iron absorption, if taken with ascorbic acid or an iron supplement
providing pharmacological doses or if iron is consumed as the “heme” component of
hemoglobin and myoglobin from meat, poultry or fish (40% heme iron, 60% non-heme
iron). In addition, tea does not affect non-heme iron absorption as much when the two are
consumed separately by rats, with between 60-70% inhibition when tea is taken with
meals versus about 20% with tea is taken between meals, since rats synthesize ascorbic
acid in the gut. In humans, taking tea with food inhibited non-heme iron absorption from
68% with 0.5 g tea with 40 mg flavonoids per cup to 91% with 5.25 g tea with 420 mg
flavonoids per cup.3406
B.1.1.d & B.1.2.b P-glycoprotein (Pgp), also known as multidrug resisance protein 1 (MDR1)
or ATP-binding cassette B1 (ABCB1), in cells of the intestinal mucosa in humans is a
major factor in reducing the absorption of some drugs. Pgp is a cell membrane efflux
transport protein that pumps certain hydrophobic substrates, including some carcinogens,
out of cells lining the intestine and back into the intestinal lumen.
B.1.1.e The organic anion transporting polypeptide (OATP) also mediates drug uptake at the
intestinal level. OATP-1A2 (OATP-A) is predominantly expressed in the brain rather
than the intestine, and OATP-1B1 (OATP-C) is a liver-specific uptake transporter,
whereas OATP-2B1 (OATP-B) is more like involved with aiding in intestinal absorption.
B.1.1 Slowed and/or Reduced Absorption by Herbal Components p. 364
B.1.1.b.ii Precipitation by Non-tannin Phenols
Chili fruit (Capsicum anuum) – iron2807
Tea (green) leaves [EGCG] (Camellia sinensis) – sunitinib3210
B.1.1.d Selective Efflux of Drugs or Carcinogens by Inducing P-Glycoprotein
Chinese rhubarb root (Rheum palmatum) − phenytoin (intestine)3335
Dan shen root (Salvia miltiorrhiza) − fexofenadine (intestine)3424
Garlic bulbs (Allium sativum) − saquinavir3223
St. John’s wort flowers/leaves (Hypericum perforatum) – methadone1641
B.1.1.e Selective Inhibition of Absorption likely by Inhibiting OATP-B and/or -A
Apple fruit juice (Malus domestica) – aliskiren (2B1),3069 fexofenadine (2B1)3068
Blueberry fruit (Vaccinium spp.) – glibenclamide3084
Milk thistle seeds pc silymarin (Silybum marianum) – rosuvastatin (oocytes-1B1)2963 [not
rosuvastatin2963]
Orange fruit juice (Citrus sinensis) – aliskiren (2B1)3069
Tea green leaves (Camellia sinensis) – nadolol,3388 nadolol,3531 nadolol (kidney - 1A2)3388
84
B.1.1.f Slows and/or Decreases Active Intestinal Transport by hPepT1 and/or Others
Cranberry fruit juice (Vaccinium macrocarpon) – cefaclor (s)2618
B.1.2 Enhancement of Absorption p. 368

B.1.2.a General Absorption Enhancement by Pungent Herbals
Black pepper fruit (Piper nigrum) – calcium, iron, zinc3471
Cayenne fruit *(Capsicum frutescens) – calcium, iron, zinc3471
Ginger rhizome (Zingiber officinale) – calcium, iron, zinc3471
Long pepper fruit (Piper longum) – calcium, iron, zinc3471
B.1.2.b Selective Retention of Drugs by Inhibiting P-Glycoprotein Drug Efflux
African mistletoe leaves (Tapinanthus sessilifolius) – digoxin (intestine)3197
Barberry bark c berberine [at oral dose of 30-60 mg/kg] (Berberis spp.) – cyclosporine, digitalis
(intestine),3105 ketoconazole (intestine)3104
Bitter leaf leaves (Vernonia amygdalina) – digoxin (intestine)3197
Coptis rhizome c berberine [at oral dose of 30-60 mg/kg] (Coptis chinensis) – cyclosporine, digitalis
Garlic clove *(Allium sativum)
Aged garlic e extract and c S-allyl cysteine – c cisplatin (kidney),3140 e saquinavir [opposite for
darunavir] (liver),3141 c rhodamine 123,3142,3143 e rhodamine 123,3143 e digoxin,
hydrochlorothiazide [opposite for glibenclamide] (intestine)3142
Ginger rhizome c 6-gingerol (Zingiber officinale) – digoxin (colon, kidney)2279
Ginkgo leaves (Ginkgo biloba) – raltegravir (intestine),3190 talinolol (intestine),3138 [not
fexofenodine3135], rhodamine-123 (intestine)3192
Goldenseal roots/rhizome c berberine [at oral dose of 30-60 mg/kg] *(Hydrastis canadensis) –
cyclosporine, digitalis (intestine),3105 ketoconazole (intestine)3104
Licorice root pc glabridin, c glycyrrhetinic acid (Glycyrrhiza glabra) − daunorubicin, vinblastine3368
Lobelia herb c lobeline (Lobelia inflata) – rhodamine-123, doxorubicin (colon, leukemia)3442
Milk thistle seeds pc silymarin (Silybum marianum) – talinolol (intestine)3137 [not digoxin1806] [See Note
3.]
Mulberry twigs pc morin (Morus alba) – paclitaxel (intestine)2834
Nan wu wei zi fruit (Schisandra sphenanthera) ‒ tacrolimus (intestine),2829 paclitaxel (intestine),2827
tacrolimus (intestine),2828,2830 tacrolimus (colon)2830
Onion bulbs c quercetin (Allium cepa) ‒ fexofenadine,3134 paclitaxel (intestine)2835
Oregon grape root bark c berberine [at oral dose of 30-60 mg/kg] (Mahonia spp.) – cyclosporine, digitalis
Papaya leaves (Carica papaya) – digoxin (intestine)3197
Schisandra fruit lignans or c schisandrin B (Schisandra chinensis) – talinolol (intestine),3138 daunorubicin
(leukemia, epidermoid carcinoma, breast cancer MCF-7 & Bcap37), doxorubicin (leukemia,
epidermoid carcinoma), epirubicin (leukemia, epidermoid carcinoma), homoharringtonine
(leukemia, epidermoid carcinoma), hydroxycamptothecin (leukemia, epidermoid carcinoma),
mitoxantrone (leukemia, epidermoid carcinoma), taxol (leukemia, epidermoid carcinoma, breast
cancer MCF-7 & Bcap37), vincristine (leukemia, epidermoid carcinoma, breast cancer MCF-7 &
Bcap37)2831
Soy beans pc genistein (Glycine max) – paclitaxel (intestine)2833
Tea green leaves pc catechins/EGCG (Camellia sinensis) – doxorubicin (intestine),3207 nicardipine
(intestine),3209 tamoxifen (intestine),3206 verapamil (intestine),3208
Turmeric root tincture or pc curcumin (Curcuma longa) – calcein-AM (colon),2777 celiprolol (intestine),2778
daunorubicin (colon),2777 digoxin (colon),2779,2780 and (kidney),2779 rhodamine-123 (colon)2777,2780 [See
Note 5.]
Notes:
85
3. Silymarin at 420 mg daily for 14 days inhibits Pgp efflux of talinolol in 18 healthy humans equal in
numbers for homozygous (CC, TT) and heterozygous (CT) MDR1 3435.3137 However, when
tested with the Pgp substrate digoxin in 16 healthy humans 440 mg silymarin in 900 mg
standardized extract daily for 14 days did not significantly alter the drug bioavailability. There
was a tendency toward reducing digoxin levels, suggesting potential Pgp induction.1806
5. While curcumin has consistently shown inhibition to Pgp in vitro2777,2779,2780 and in an in vivo study in
rats,2778 and hydroethanolic extracts of Curcuma longa and of other Curcuma spp. inhibits Pgp in
vitro,2777 methanolic extracts of C. longa and of other Curcuma spp. increased Pgp activity in
vitro.2780
B.1.2.c Enhanced Retention of Drugs by Inhibiting MRPs

Chinese rhubarb root (Rheum palmatum) − phenytoin (kidney MRP2)3335 [Note 1.]
Notes
1. The induction of Pgp by Chinese rhubarb root in rats led to significant reduction in phenytoin
bioavailability, in spite of the inhibition of MRP2 in kidney cells that would increase reaborption
of phenytoin.3335
B.1.3 No Influence on Drug Absorption in Humans

B.1.3.a No Effect on P-glycoprotein Efflux
Echinacea whole plant (Echinacea purpurea) – fexofenadine3099
Ginkgo leaf extract (Ginkgo biloba) − digoxin,3225 fexofenadine3228
B.1.3.b No Effect on OATP transport ^
Garlic clove c allicin *(Allium sativum) – pravastatin3223
B.3 Potentiating Sedative or Tranquilizing Medicines p. 373

Some sedative herbs or extracts have shown sedative and/or anxiolytic effects in animal or human
research that did not involve potentiating barbiturates, as indicated by reference citations following their
scientific names. On this basis there exists a potential interaction with other pharmaceutical sedatives,
tranquilizers, hypnotics, or depressants.
B.3.1 Hypnotic and/or Anxiolytic Drug Enhancement p. 373
3127
Licorice root (Glycyrrhia uralensis) B, BDZ
Passion flower herb (Passiflora incarnata)2879
Peppermint leaf oil (Mentha piperita) B3113
Purple passion fruit leaves (Passiflora edulis) B2952
Southern schisandra fruit (Schisandra sphenanthera) B2074
Silk tree bark (Albizia julibrissin) B, A, O3127
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) B3220
B.4 Modifying Blood Sugar In Diabetics p. 374

In the United States from 2007 to 2009, nearly a quarter of an estimated 100,000
emergency hospitalizations annually from adverse drug events in patients over 65 years of age
involved insulin (13.9%) or oral hypoglycemic agents (10.7%). These were two of the top four
categories of drugs associated with elderly emergency hospitalization due to medications, along
with warfarin (33.3%) and oral antiplatelet agents (13.3%).3023 B.4.1 Insulin-dependent diabetics
(type I) must monitor their blood sugar carefully to not only prevent high blood sugar but to
avoid causing hypoglycemic episodes as well. The combined effect of large doses of
hypoglycemic herbs with insulin treatment may lower blood sugar levels excessively and could
potentially result in insulin shock. The plants listed here have a documented ability to lower
86
blood sugar levels through a variety of mechanisms when they or their components are given
orally to humans and/or animals. The reduction of blood sugar by the botanicals listed below
has been documented for the herb (h), its juice (j), other extracts (e), and/or its components (c).
Only the antihyperglycemic or hypoglycemic effects shown in humans are specifically
designated in bold, affecting diabetics of undetermined type (db), type I (t1), type II (t2), or
healthy (hl) individuals.
B.4.2 The hypoglycemic and/or antihyperglycemic herbs are usually administered in type II
diabetes (non-insulin-dependent) to help control blood sugar which does not respond well to
insulin or oral hypoglycemic treatment. Certain botanicals taken orally with oral
hypoglycemic drugs have been shown to reduce blood sugar in humans with type II diabetes
more than by using the drug alone. While the risk of severe hypoglycemia is greater with insulin
use for type 1 diabetes, severe hypoglycemia can also occur in type II diabetes, especially in
association with multiple diabetic medications.3289 Therefore, the use of hypoglycemic botanical
prepartions by diabetics taking insulin and/or oral hypoglycemic drugs carries a risk, along with
a potential for benefitting poorly controlled glycemia. Those botanicals not having strong
hypoglycemic properties alone, such as psyllium and milk thistle, likely have an even greater
margin of safety.
B.4.1 Hypoglycemic and/or Antihyperglycemic Herbals p. 375
Bitter melon fruit (Momordica charantia)3217 − j(t2)3476
Cayenne fruit *(Capsicum frutescens) – h(hl)2808
Chirata herb (Swertia chirayita)3217
Fenugreek seeds (Trigonella foenum-graecum)3217 – h(t1)1646
[Note CORRECTION: the superscript after h(t1) is "1646", not 1645.]
Gulancha stem (Tinospora cordifolia)3217
Gymnema leaves (Gymnema sylvestre)3217
Gynostemma herb (Gynostemma pentaphyllum) ‒ e(t2)2811
Indian stinging-nettle herb (Tragia involucrata)3217
Ivy gourd herb (Coccinia indica)3217
Jambolan seeds (Syzygium cumini = Eugenia jambolana)3217
Kino heartwood (Pterocarpus marsupium)3217
Moringa stem bark (Moringa oleifera)3217
Prickly pear stems (Opuntia spp.)2826
Tulsi herb (Ocimum tenuiflorum = Ocimum sanctum)3187,3188,3189,3219
B.4.2 Antihyperglycemic Botanicals Enhancing Oral Hypoglycemic Drugs in Humans p. 378
Cassia bark extract (Cinnamomum cassia) – metformin and/or sulfonylureas1900,2758 including
gliclazide3244
Fenugreek seeds (Trigonella foenum-graecum) – glyburide(glibenclamide)130 and/or metformin961,1645
and/or glipizide;1645 sulfonylureas1360,2815 and/or biguanides1360
Garlic cloves (Allium sativum) – metformin3089
Gynostemma herb (Gynostemma pentaphyllum) – gliclazide3237
Maitake mushroom fruiting bodies (Grifola frondosa) – glyburide, glipizide, metformin1609
Milk thistle fruit (Silybum marianum) − glyburide (glibenclamide), metformin2041
Psyllium seed husks (Plantago ovata) – glyburide (glibenclamide),2798 metformin,2799 oral
hypoglycemics,2801 sulfonylureas,2800 tolbutamide2798
Royal sun agaricus mushrooms (Agaricus blazei) – gliclazide, metformin2215
Tulsi seed (Ocimum tenuiflorum = Ocimum sanctum) − chloropropamide, glibenclamide, glipizide,
penformin3308
B.5 Modifying the Effects of Anticoagulants p. 379

87
In the United States from 2007 to 2009, almost half of an estimated 100,000 emergency
hospitalizations annually from adverse drug events in patients over 65 years of age involved
warfarin (33.3%) or oral antiplatelet agents (13.3%). These were two of the top three categories
of drugs associated with elderly emergency hospitalization due to medications, along with
insulin (13.9%).3023
B.5.1.b Anticoagulant effects can be produced by a variety of marine algae polysaccharides. Red
algae containing certain sulphated polysaccharides, especially lambda-carrageenan which has
1/10 the potency of heparin, inhibit thrombin both directly and indirectly. Carrageenan, though
antipeptic, is contraindicated in the treatment of peptic ulcer, and carrageenan sources should be
avoided in any GI bleeding to avoid exacerbating the hemorrhaging. Brown algae contain
various fucan sulphated polysaccharides (fucoidans) that form tertiary complexes with ATIII-Xa
and ARIII-IIa, based on a high degree of sulfation, and inactivate thrombin directly or indirectly
by heparin co-factor II.3345 This has been shown to occur in both in vitro and in vivo when the
polysaccharide components are injected. These active polysaccharides have not been shown to
be systemically active after oral consumption, but local anticoagulant effects in the gut may be
possible. The research on marine algae is mostly studies using platelet-rich plasma in vitro (I) to
test an extract/fraction (e) or one or more isolated components (c). In vivo (V) studies use
injections in animals test these derivatives for enhancement of bleeding time or protective effects
against a clot-inducing agent.
B.5.1.c In association with simultaneous consumption of the common anticoagulant, several
herbs have been inferred from in vivo studies or human case reports to possibly induce a
reduction in the metabolism and/or enhancement of the effect of warfarin (W) or antiplatelet
drugs (AP), leading to increased risk of hemorrhage. Decreased plasma neutralization of
heparin (H) has also been documented. Risk of hemorrhage is considered possible when
combining these drugs with certain herbs such as garlic, Asian ginseng, and/or ginkgo.3525,3526
However, this is not supported by in vivo evidence in regard to their effects on platelet
function.2262
B.5.1 Increasing Potential for Hemorrhage p. 382
B.5.1.a Additive Effect Due To Content of Potential Prothrombinopenic Components
Sanchi ginseng steamed roots (Panax notoginseng) Vh3450
B.5.1.b Commonly Consumed Marine Algae with Antithrombin Polysaccharides
Bladderwrack brown algae (Fucus vesiculosus) Ic735,737,3345
Ma-kombu thallus (Laminaria japonica) Ie, Ve2840
Sugar kelp brown algae (Saccharina latissima = Laminaria saccharina) Ic3345
B.5.1.c Warfarin or Heparin Metabolism Inhibitors and/or Anticoagulant Adjuvants
[Note CORRECTION: Cocoa seed (Theobroma cacao)1447 belongs in B.5.1.d., rather than B.5.1.c.]
Ginkgo leaves (Ginkgo biloba) [neg W & AP2960]
Lycium [Gobi] fruit (Lycium barbarum) We1768,3027,3448
B.5.1.d Platelet Aggregation &/or Adhesion Inhibitors
Chokeberry fruit (Aronia melanocarpa) Ie,2961,2964,3128,3258 Ee2964,3257
Cocoa seed (Theobroma cacao) Ee1447,2906
Grape seed (Vitis vinifera) Ie2961,3128
Sanchi ginseng steamed roots (Panax notoginseng) Ic,3451 Ie,3450,3451 Eh3450
B.5.1.e Fibrin Formation Inhibitors or Fibrinolysis Promoters
Chokeberry fruit (Aronia melanocarpa) Ie3128
Ginger root (Zingiber officinale) HSh3449
Grape seed (Vitis vinifera) Ie3128
88
B.5.2 Increasing Potential for Coagulation p. 385
B.5.2.b Warfarin Antagonism by Inducing Its Metabolism and/or Modifying Its Effect
American ginseng root (Panax quinquefolius) HS1600
Avocado fruit (Persea americana) CR3123
B.7 Modifying Enzyme Activities in Metabolic Conversions p. 387

Phase II conjugation and rate of clearance of conjugates can be reduced by liver diseases
and vary with their severity. For example, hepatitis C virus cirrhosis and nonalcoholic fatty liver
disease (NAFLD) patients show significant 4.7-fold and 3.3-fold higher total (unconjugated and
conjugated as glucuronides or sulfates) silymarin flavonolignan blood levels, respectively, than
healthy subjects.3025 NAFLD patients have significantly higher unconjugated flavonolignan
levels than those with noncirrhotic hepatic C. Metabolism of individual flavonolignans also
varies between disease conditions, and this leads to disproportionate bioavailability in
comparison with the oral dosage concentrations.3026
B.7.1.a The testing of botanical effects on metabolic conversions both in vitro and in vivo
almost never involves use of the whole powdered herb. In vitro evaluation requires extraction of
the herb for adequate cellular and enzymatic exposure. In vivo tests, whether human (in bold) or
animal (in italics), also involves dosing in forms that are typically liquid or solid extracts or
fractionated derivatives of the herb. There are many different types of extracts for each herb, and
these vary in composition and activity. Since each separate form cannot be individually
designated in this table format, they are simply described by the common and scientific names of
the herbs (which are capitalized). The specific form used for in vivo studies will usually be
described in the main body of the text under the common name of that herb, especially for
human studies. When chemical fractions or isolated derivatives (indicated with only small
letters) are studied, this noncapitalized term for the fraction or isolated constituent is given along
with the names of the herb(s) from which is it can be derived.
A preliminary outline of substrates, i.e., drugs, hormones, and procarcinogens, is initially
listed. Following each substrate, the abbreviations of those herbs or their components are listed
alphabetically in one of the two groups, depending on whether they increase (inhibit metabolism
or efflux) or decrease (induce metabolism or efflux or reduce transport) that substrate. The
inhibitors are to the left and inducers are to the right. If both inhibitors and inducers are listed for
a drug, hormone, or procarcinogen substrate, these groupings are separated with a semicolon.
The specific type of pharmacokinetic interactions covered in this section are those for which the
mechanism is not definitely known. So, the isozymes and conjugating enzymes shown to
inhibited or induced are noted following the herbs or components in those lists. Efflux or
transport proteins/polypeptides like Pgp or OATP-C alter bioavailability; inhibiting intestinal
Pgp increases intestinal absorption and thereby increases bioavailability, whereas inhibiting
OATP-C (OATP-1B1) reduces hepatic uptake which decreases substrate metabolism and
increases bioavailability. On the other hand, inhibiting intestinal OATP-B (OATP-2B1) reduces
intestinal absorption and bioavailability. Studies in which contradictory results with herbals were
negative [neg] for inhibiting enzymes conversions in humans are shown in brackets, while
other findings that contradict each other based on types of studies or differences in preparations
are discussed in the "Notes" at the end of this section.
B.7.1.b Gene activation via the nuclear transcription factor pregnane X receptor
(PXR) regulates phase I isozymes CYPS 1A2, 2B6, 2C8,9,19, and 3A4,5,7, phase II enzymes
UGTs (1A1, 1A3, 1A4, 1A6, 1A9),3045 GSTs (A1, A2), and STs, and phase III drug
transporter proteins Pgp (MDR1), MRP-2 and OATP.1928 However, ginkgo extract and
89
ginkgolides A and B were shown to be potent activators of PXR and induce CYP2B6, CYP3A4,
UGT1A1, MRP2, and MDR1 in human primary hepatocytes in vitro,3044 but in human studies
oral ginkgo extract inhibited MDR12680 and inhibited,1728,2015 had no effect,1328,1824,2301 or slightly
induced1840 CYP3A4, while other in vitro found CYP3A4 inhibition.1823,2145,2151,2292,2608 Human
studies and the particular parameters that they investigate (e.g., preparation, dose, duration)
remain the most clinically relevant for providing data on pertinent metabolic impacts.3045
B.7.1.d Another transcription factor acting as a nuclear receptor gene activator that
impacts xenobiotic metabolism is the constitutive androstane receptor (CAR). CAR regulates
expression of CYPs 2A6, 2B6, 2C9,19 and 3A4, phase II UGTS (1A1, 2B1)3045 and GST-A & -
M, and phase III MDR-1. The hepatic nuclear factor 4 determines the liver’s PXR and CAR
induction of CYP3A4. Known CAR-mediated inducers of CYP3A4 are the praeruptorins A, C
and D from qian hu (Peucedanum praeruptorum) root.3334
B.7.2 [Note: CORRECTION of the web address listing CYP isozyme substrates, inhibitors, and
inducers is: http://medicine.iupui.edu/clinpharm/DDIs/table.aspx .1567]
B.7.3 Inducers or inhibitors of phase II conjugation reactions are listed along with organ
sources of the enzymes that have been used in the cited research studies. Genetic polymorphisms
are also found in humans for phase II enzymes such as glutathione S-transferases (GSTs) that
exist in the primary classes alpha, pi, mu, theta, and zeta (A, P, M, T, and Z, respectively). UDP-
glucuronosyltransferase (UGT) is made up of three main subfamilies with 18 enzyme
polymorphisms, UGT1A (1,3-10), UGT2A (1,2), and UGT2B (4,7,10,11,15,17,28), most
expressed in the liver but some (1A7, 1A8, 1A10) only in the intestines. The influence by
inducers and inhibitors on the specific classes and families of these conjugating isozymes are
noted when known. Specific probe substrates are used for UGT 1A1 (bilirubin, estradiol,
etoposide), 1A4 (imipramine, midazolam, trifluoperazine), 1A6 (naphthol, serotonin), 1A9
(propofol, phenylbutazone), 2B7 (morphine, 3'-azidothymidine, naloxone), and 2B15 (S-
oxazepam).3322
B.7.4 Herbal influences on steroid metabolism are included to indicate both potential
interactions with pharmaceuticals as well as possible modulation of endogenous hormones that
impact systemic function. Therapeutic application of modified steroid conversion is illustrated by
herbs that reduce the estrogen to testosterone ratio through inhibition of the enzyme aromatase
[CYP 19; B.7.4.a] and have effectively been used in the treatment of benign prostatic hyperplasia
(BPH), while pharmaceutical aromatase inhibitors are used to treat postmenopausal hormone-
dependent breast cancer. Similar approaches have be used in other hormone-dependent
conditions typified by imbalanced hormone ratios, such as using 5-reductase inhibitors (type
1 or type 2) [B.7.4.b] to treat BPH and/or help prevent prostate cancer for those in whom it has
not yet been detected. The influence on sterol 27-hydroxylase [CYP27A1; B.7.4.j] in the liver
for cholesterol conversion to bile acids and for vitamin D3 bioactivation also has important
implications, as this enzyme is regulated by a variety of endocrine hormones.
B.7.1.a Modulation by Phase I &/or Phase II &/or Phase III

Probes: benzyloxyresorufin [2B1/2/6] – cc2938
7-ethoxyresorufin [1A1/2] − ; Co3290
7-pentoxyresorufin [2B1/2] – ; An,2975 Co3290
Drugs: rosuvastatin – bc3232
phenytoin − Gc3284 ; Bc, Fg3284
warfarin – ; Co,3290 Gb3529
Steroids: dehydroepiandosterone [OATP-C] − bA, ep mr, nr, si3224
90
estradiol – Bl, By, ea3082
testosterone – ; Co3290
Procarcinogens: benzo[a]pyrene [1A1] – ep 3201
Conversion/Clearance Inhibitors (Increase Bioavailability)

(Ao) Aloe gel (Aloe vera) – 2C112947
(bA) biochanin A from red clover leaves, flowers (Trifolium pratense), etc. − OATP-C3224
(Bl) Blueberry fruit (Vaccinium corymbosum) – 1A1, 1B13082
(Bc) Black cumin seed (Nigella sativa) – CYP 2B11, 3A43284
(By) Black raspberry fruit (Rubus occidentalis) – 1A1, 1B13082
(cc) curcumin in turmeric root (Curcuma longa, Curcuma aromatica) – 1A1,2035 1A2, 2B6, 2C9, 2D6,
3A42938
(ea) ellagic acid as in strawberry leaves and seeds (Fragaria spp.), raspberry seeds and leaves (Rubus
spp.), black walnut leaves and nuts (Juglans nigra), etc. – 1A1,3082
(ep) epigallocatechin gallate [EGCG] from green tea leaves (Camellia sinensis) – OATP-C;3224
1A1/1A2,1998,3201 2A6,2C19, 2E1, 3A43201
(Gb) Ginkgo leaf extract (Ginkgo biloba) – [not CYP2B6 (bupropion)2762]; UGT-1A93191
(Gc) Garden cress seed (Lepidium sativum) – CYP 2B11, 3A43284
(mr) myricetin as in tea (black and green) leaves (Camellia sinensis), parsley leaves (Petroselinum
sativum), cranberry fruit/juice (Vaccinium macrocarpon), etc. – OATP-C3224
(my) myristicin from parsley leaf oil (Petroselinum sativum), nutmeg seed *(Myristica fragrans), etc. –
1A1, 1A2, 2B1,3129
(nr) naringenin as in grapefruit fruit juice (Citrus paradisi) – OATP-C3224
(si) silymarin/silibinin from milk thistle seeds (Silybum marianum) – OATP-C3224
Conversion/Clearance Inducers (Reduce Bioavailability)
(An) Andrographis leaves (Andrographis paniculata) − 1A1, 2B2975 [See Note 9.]
(bc) baicalin/baicalein and other Chinese skullcap flavones (Scutellaria baicalensis) – OATP-
1B1(*1b/*1b or*1b/*15)3232
(Co) Coleus root (Coleus forskohlii) − CYP 1A1/2, 2B, 2C, 3A3290 ; GST3290
(Ep) Echinacea purpurea tops (Echinacea purpurea) − OATP-B;1883 1A1, 2D12978
(Fg) Fenugreek seed (Trigonella foenum-graecum) – CYP 2B11, 3A43284
(Gb) Ginkgo leaf extract (Ginkgo biloba) – OATP-B;1883 PXR; 2B6, 3A4,3044 2B, 2C3529 [not CYP2B6
(bupropion)2762] ; GST-P1,3226 UGT-1A13044
(gf) ginkgo flavonol aglycones in ginkgo leaves (Ginkgo biloba) – CYP 1A2; UGT1A13044
(gi) glucobrassicin indole metabolites in specific crucifers (Brassica oleracea) –1A1, 1A2, 2B,3129
(go) ginkgolides A&B in ginkgo leaves (Ginkgo biloba) – PXR; 2B6, 3A4; UGT3192
(Kv) Kava root (Piper methysticum) – 1A2, 2B1, 3A13362 [Note 10.]
(pi) phenethyl isothyocyanate from watercress herb (Nasturtium officinale), crucifers (Brassica spp.) –
1A1, 1A2, 2B,3129
Notes:
9. Though andrographis has shown inhibition of the metabolism of probe substrate 7-ethoxyresorufin for
CYP 1A1/2 in vitro,2035 it induces metabolism of this probe in vivo in rats. No effect was shown
on the in vivo metabolism of the CYP 1A2 probe substrate methoxyresorufin.2975
10. While in vitro metabolism by CYP of substrates of CYP 1A1,1733 1A2, 2C19,1327,1733 2C8,2568
2C9,1327,1577,1733 2C19,2568 2D6,1327 3A4,1327,1475,1577,1733 4A9/111327 was inhibited, when 1.0 or 2.0
g/kg of kava extract was administered to rats daily for 14 weeks, CYPs 1A2, 2B1, and 3A1
showed increased expression in both males and females. No effect on CYP isozymes or GGT
activity was seen below the 1.0 g/kg. No adverse effects were seen at 0.25 mg/kg.3362
B.7.1.b Influence on Pregnane X Receptor (PXR)
Receptor activators
(Cf) California poppy aerial parts [ethanolic extract] (Eschscholzia californica) – (liver)3546
91
(ez) escholtzine from California poppy aerial parts [ethanolic extract] (Eschscholtzia californica) –
(liver)3546
(Gb) ginkgo leaf extract (Ginkgo biloba) − (liver)3044
(gf) ginkgo flavonol aglycones in ginkgo leaves (Ginkgo biloba) – liver3044
(go) ginkgolides from ginkgo leaf (Ginkgo biloba) − (liver)3044
B.7.1.c Influence on Aryl hydrocarbon Receptor (AhR)
Receptor inhibitors
(lt) luteolin as in thyme herb (Thymus spp.), asparagus stem (Asparagus officinalis), etc. – liver, breast3366
Receptor activators
(gf) ginkgo flavonol aglycones in ginkgo leaves (Ginkgo biloba) – liver3044
B.7.1.d Influence on Constitutive Androstane Receptor (CAR)
Receptor inhibitors
Guggul (Commiphora mukul) resin2111,2112
Receptor activators
Qian hu (Peucedanum praeruptorum) root3334
B.7.2 Influences of Herbal Agents in Phase I on Specific Cytochrome P450 Isozymes p. 405
B.7.2.a Influence on CYP 1A2 Metabolic Conversion of Substrates
Probes:7-methoxyresorufin – cc2938 ; Co,3290 gi, pi3129
Drugs: caffeine – ; rs,2970 SJ1328
phenacetin – ts2770
Procarcinogens: 2-amino-1-Me-6-Ph-Imidazo-[4,5b]Pyridine (PhIP) − ep3201
Isoenzyme Inhibitors
(cc) curcumin in turmeric root (Curcuma longa, Curcuma aromatica)
(ep) epigallocatechin gallate [EGCG] from green tea leaves (Camellia sinensis)
(ts) tanshinones from dan shen roots (Salvia miltiorrhiza)
Isoenzyme Inducers
(Co) Coleus root (Coleus forskohlii)
(gi) glucobrassicin indole metabolites in certain crucifers (Brassica oleracea)
(pi) phenethyl isothyocyanate from watercress herb (Nasturtium officinale), crucifers (Brassica spp.)
(rs) resveratrol as in dark-skin grapes (Vitis vinifera), mulberry fruit (Morus spp.), blueberry fruit
(Vaccinium spp.)
(SJ) St John's wort herb (Hypericum perforatum)
No Effect in Human Studies with Isoenzyme CYP 1A2 substrates p. 408
[Note CORRECTION: (SJ) St John's wort herb (Hypericum perforatum) – caffeine superscript '1328'
should be deleted, since a significant mean 26% increase in metabolite to caffeine ratio was
observed in the group of 6 men and 6 women. Also, apply this CORRECTION to Note 3.]
(bb) berberine as in barberry (Berberis vulgaris), coptis (Coptis spp.), goldenseal *(Hydrastis
canadensis), and Oregon grape (Mahonia spp.) roots/barks − caffeine3238
(Gb) Ginkgo leaf extract (Ginkgo biloba) – caffeine1328,1808,2302,3091 [See Note 4.]
(La) English lavender flowers (Lavandula angustifolia) – caffeine3303
(Te) Tea (green) leaf catechin extract (Camellia sinensis) – caffeine2810
Notes:
4. Ginkgo extract is a CYP1A2 inducer at low concentrations (2.2 mcg/ml) but an inhibitor at higher
concentrations (22 and 220 mcg/ml) in vitro.2292 At 100 mg/kg orally and as 0.5% of the diet in
rats it was shown to induce this isozyme,1952,2278 but normal therapeutic doses do not produce this
effect in humans.1328,1808,2302,3091
7. The study with 42 healthy humans showing significant induction of caffeine metabolism involved
taking 1 gm of resveratrol orally once daily for 4 weeks.2970 Consumption of smaller doses may
92
not have this effect, and this 1 gm/day resveratrol dosage could not reasonably be maintained for
a month by eating the whole fruit of grapes, blueberries, and/or mulberries.
B.7.2.b Influence on CYP 2E1 Metabolic Conversion of Substrates

Probes: aniline – Am2857
Drugs: chlorzoxazone – ts2770
Procarcinogens: NMBA (N-nitrosomethylbenzylamine) – Bp2460
(Am) Amla fruit (Emblica officinalis)
(Bp) Black raspberry fruit (Rubus occindentalis)
Notes:
1. SJW extract (0.3% hypericin) at 900 mg daily for 28 days in 6 men and 6 women in good health
increased chlorzoxazone CYP2E1 metabolism by 110%,1328 but in 12 healthy elderly the same
preparation and dosage increased chlorzoxazone metabolism by only 28%.1808
B.7.2.c Influence on CYP 3A Metabolic Conversion of Substrates

Probes: 7-benzyloxy-4-(Fl3Me)coumarin – cc,2938 Cf,3546 ez,3546
7-benzyloxyquinoline − cc2938
7-benzyloxyresorufin – cc2938
dibenzylfluorescein – cc2938
luciferin 6'benzyl ether – sc2771
Drugs: atazanavir − Cc 3520
atorvastatin – ; SJ2200
buspirone ‒ rs,2970 Te2810
diazepam ‒ Cc3519 ; Eu3519
efavirenz − Gb 3392
erythromycin − Gf,2590 sc2946

finasteride − ; SJ3133
methadone – ; SJ1641
midazolam – bb, 3238
cc, 2778
cc, 2279
Ds, 3425
ep, 3201
gn 2779
Pm,3113 sc,sc,2832 Sf,1923 Ss,3136 Te,3202
Wg1885 ;
Ds,3425,3443 Ep,3099 Gb,3135
2965 2832
Gs, sc,
nevirapine – pp3132 ; SJ1972
nicardipine – ep 3209
nifedipine – Gb3229
nitrendipine − Pg3111
paclitaxel – Eu,2568 Fr,2664 Gb,2145 Gf,2568 Go,2145 is,2833 kb,2664 Kv,2568 Mt,2145 Po,2568 qu,2835
Ss2827
ritonavir − Cc3520
saquinavir − Cc3520
sirolimus − Gf3144
tacrolimus – Gf,3124 Ss,2830 Ss,2828,2830 Ss2829
tamoxifen − ep3206
Steroids: testosterone – cm,2768 sc,2946 ts2770 ; Co3290
cortisol – Gf 3021,3426
Procarcinogens: aflatoxin B1 − ep3201

93
canadensis), and Oregon grape (Mahonia spp.) roots/barks [See Note 10.]
(Bo) Bitter orange fruit juice (Citrus aurantium)
(Cc) Cat’s claw bark (Uncaria tomentosa)
(Cf) California poppy aerial parts [ethanolic extract] (Eschscholzia californica)
(cm) curcumenol from zedoary rhizomes (Curcuma zedoaria)
(Ds) Dan shen root (Salvia miltiorrhiza) [See Note 22.]
(ep) epigallocatechin gallate [EGCG] from green tea leaves (Camellia sinensis)
(Ep) Echinacea purpurea tops (Echinacea purpurea) [See Note 3.]
(Eu) Eucalyptus leaf oil (Eucalyptus globulus)
(ez) escholtzine from California poppy aerial parts [ethanolic extract] (Eschscholtzia californica)
(Fr) Frankincense resin (Boswellia spp.)
(Gb) Ginkgo leaf extract (Ginkgo biloba) [See Note 15.]
(Gf) Grapefruit fruit/juice (Citrus paradisi) [in humans, intestinal CYP3A4 only] [See Note 14.]
(gn) 6-gingerol in ginger root/rhizome (Zingiber officinale)
(Go) Goldenseal root and herb *(Hydrastis canadensis) [See Note 10.]
(is) isoflavones as in soy beans (Glycine max), kudzu plant (Pueraria lobata), red clover herb (Trifolium
pratense), etc.
(kb) keto boswellic acids from frankincense resin (Boswellia spp.)
(Kv) Kava root *(Piper methysticum) [See Note 9.]
(Mt) Milk thistle seeds (Silybum marianum) [See Note 1.]
(Pg) Pomegranate fruit (Punica granatum) [See Note 16.]
(Pm) Peppermint leaf (Mentha piperita)
(Po) Pomelo fruit juice (Citrus grandis)
(pp) piperine in black pepper fruit (Piper nigrum), long pepper fruit (Piper longum)
(qu) quercetin as in onion bulbs (Allium cepa), tea leaves (Camellia sinensis), cranberry fruit/juice
(Vaccinium macrocarpon), etc.
(Vaccinium spp.)
(sc) schisandrol/gomisin lignans from schisandra fruit (Schisandra chinensis) [See Note 20.]
(Ss) Southern schisandra fruit (Schisandra sphenanthera)
(Te) Tea (green) leaf catechin extract (Camellia sinensis) [See Note 19.]
Isoenzyme Inducers
(Ds) Dan shen root (Salvia miltiorrhiza) [See Note 22.]
(Ep) Echinacea purpurea tops (Echinacea purpurea) [See Note 3.]
(Eu) Eucalyptus leaf oil (Eucalyptus globulus)
(Gs) Asian ginseng root (Panax ginseng) [See Note 11.]
(sc) schisandrol A/gomisin A lignans from schisandra fruit (Schisandra chinensis) [See Note 20.]
(SJ) St. John’s wort herb (Hypericum perforatum)
No Effect in Human Studies with Isoenzyme CYP 3A substrates
(Ca) Cannabis tops infusion *(Cannabis sativa, Cannabis indica) – docetaxel, irinotecan2941
(Ep) Echinacea purpurea root or entire plant (Echinacea purpurea) – darunavir/ritonavir,2793 etravirine,3538
lopinavir/ritonavir3099 [See Note 3.]
(Ga) Garlic bulbs (Allium sativum) − simvastatin3223 [See Note 7.]
(Gb) Ginkgo leaf extract (Ginkgo biloba) – anastrozole, letrozole,3268 lopinavir,3135 midazolam,3091
ritonavir,3135 tamoxifen,3268 ticlopidine3227 [See Note 15.]
(La) English lavender flowers (Lavandula angustifolia) – midazolam3303
94
Notes:
3. While midazolam metabolism was induced by 750 mg daily for 28 days of an 8:1 standardized fresh
whole plant extract, lopinavir metabolism was not affect after 14 days of the extract when given
in combination with the CYP 3A inhibitor ritonavir.3099 Etravirine metabolism was not
significantly impacted by 500 mg of the root extract every 8 hours for 14 days in 15 HIV-infected
patients on a stationary 400 mg daily drug dosage.3538 CYP3A1/2 in rats was inhibited by 50
mg/kg of a 60% ethanolic extract of E. purpurea herb after 3 days.2978
7. 7. Garlic caplets reduced plasma content of saquinavir by 50% possibly by induction of CYP3A4.1210
However, when 600 mg garlic extract was taken by 10 men twice daily for 21 days, though it
decreased the average saquinavir bioavailability by 15%, it did not change bioavailability of
CYP3A4 substrate simvastatin. The CYP3A4 expression was reduced by only 13%, but intestinal
P-glycoprotein increased by 31%. So, since saquinavir is a substrate of both CYP3A4 and Pgp,
the induction of Pgp best explains the decreased saquinavir levels, in spite of 13% less
metabolism by CYP3A4.3223
10. Goldenseal extract at 2.7 gram daily inhibited midazolam metabolism in 12 men and women.1807
Likewise, 0.9 grams of berberine daily for 14 days significantly increased single-dose midazolam
bioavailability and half-life in 17 healthy men.3238
11. Daily doses for 28 days of 1.0 gm Asian ginseng standardized to 5% ginsenosides induced
metabolism of the CYP3A4 substrate midazolam,2965 while 1.5 gm failed to alter the 1-hour
postdose ratio of metabolite to drug for midazolam in 2 human studies.1328,1808 However, 200
mg/day of uncharacterized "ginseng" for 18 days inhibited metabolism of CYP3A4 substrate
nifedipine, as indicated by increased peak plasma concentrations of 29%.1728
15. Concerning ginkgo, 360 mg/day EGb 761 increased midazolam bioavailability by 25%.2015
However, 240 mg standardized ginkgo failed to alter the metabolism of CYP3A4 substrate
midazolam in humans.3091 In a study of 20 patients each taking the hormonal CYP 3A4 substrates
anastrozole, letrozole, or tamoxifen, there were no significant changes in trough concentration
after taking 240 mg daily of EGb 761 for 3 weeks.3268 Yet, in another study 240 mg daily
significantly reduced midazolam bioavailability by 34% and its maximum concentration by 31%,
but half-life was not changed, indicative of intestinal, but not hepatic, induction. Still, the same
dose for 2 weeks had no effect on the combination of CYP3A4 substrates lopinavir and ritonavir,
possibly due to ritonavir's CYP3A4 inhibiting activity.3135
16. Though pomegranate juice inhibits CYP3A in rats,1920,3111 2 doses prior to midazolam had no effect on
midazolam clearance in healthy humans.2213
19. Though a green tea catechin extract supplying 844 mg catechin daily for 14 days to 11 healthy
humans did not affect alprazolam metabolism,1710 use of a green tea catechin extract supplying
800 mg EGCG daily for 4 weeks to 42 healthy human subjects led to a 20% increase in buspirone
bioavailability, but this change was not deemed clinically significant.2810 The inhibition effect of
green tea extract with 60%+ catechins on oral midazolam metabolism in rat intestines was
opposite its induction effect on IV midazolam in the liver of rats; the strong inhibitory effect
using human liver microsomes in vitro is therefor not reliable for predicting the in vivo effect.3202
20. The lignan extract of schisandra containing schisandrol A, gomisin C, deoxyschizandrin, and -
schizandrin inhibits CYP 3A4 metabolism of midazolam in vitro and when 1 dose is given to rats
with oral midazolam, but not IV midazolam, indicating inhibition of intestinal but not hepatic
metabolism. However, when the lignan extract is given long-term it induces the CYP 3A4 protein
expression in the liver 2.5-fold and its intestinal metabolism 4-fold, and thereby increases
midazolam metabolism, especially in the small intestines. Gomisin C was the most potent
inhibitor in vitro and the least concentrated in the liver, while schisadrol A was the least potent
and the most concentrated in the liver.2832 Though gomisins B and G are also active, gomisin C is
the most potent inhibitor of CYP3A4 metabolism of erythromycin and testosterone in vitro and
irreversibly inactivates it in a time- and concentration-dependent manner.2946
95
21. The study with 42 healthy humans showing significant inhibition of buspirone metabolism involved
22. Though a single dose of dan shen extract led to an 87% increase in midazolam maximum plasma
concentration,3425 when the extract was given for 10 or 14 days it decreased the maximum
concentration, half-life, and bioavailability in 12 healthy men.3425,3443 Tested in vitro the
component dihydrotanshinone I inhibits CYP3A, while cryptotanshinone and tanshinone IIA
induce CYP3A.3425
B.7.2.d Influence on CYP 2C9 Metabolic Conversion of Substrates

Drugs: diclofenac – Cb,3085 cc,2938 Pg3112
flurbiprofen – am,1954 Pg,3245 qu1954
losartan − bb,3238 rs,2970 si2981
phenprocoumon – ; SJ605
rosiglitazone – ; SJ2638
tolbutamide – Pg,3112 pt,3043 ts2770
warfarin − si2980 ; Co,3290 Gb3529
canadensis), and Oregon grape (Mahonia spp.) roots/barks
(Cb) Cranberry fruit/juice (Vaccinium macrocarpon)
(Pg) Pomegranate fruit (Punica granatum)
(pt) polysacchacaride peptides from turkey tail (Coriolus versicolor)
(Vaccinium spp.) [See Note 8.]
(si) silymarin/silybin from milk thistle seeds (Silybum marianum) [See Note 8.]
Isoenzyme Inducers
(SJ) St. John’s wort herb (Hypericum perforatum)
No Effect in Human Studies with Isoenzyme CYP 2C9 substrates
(Cb) Cranberry fruit/juice (Vaccinium macrocarpon) – diclofenac3085 [See Note 9.]
(Gb) Ginkgo leaf extract (Ginkgo biloba) – tolbutamide2011,3091 [See Note 3.]
(La) English lavender flowers (Lavandula angustifolia) – tolbutamide3303
(Pg) Pomegranate fruit (Punica granatum) − flurbiprofen3245
(Te) Tea (green) leaf catechin extract (Camellia sinensis) – losartan2810
Notes:
3. Though ginkgo extract acts as a CYP 2C9 inhibitor in vitro,2011,2145,2151 at 360 mg/day EGb 761 in
humans2015 and in rats it was shown to induce this isozyme.1952,3529 Normal therapeutic doses do
not produce either effect in humans.1433,1774,1842,2011,3091
7. The study with 42 healthy humans showing significant inhibition of losartan metabolism involved
8. The inhibition of losartan metabolism by a 14-day treatment with 140 mg of silymarin 3 times daily
was only significant in the 6 Chinese men with a CYP2C9*1 genotype; it was not significant in
the 6 men with a CYP2C9*3 genotype.2981
96
9. Cranberry juice inhibited the metabolism of diclofenac by human liver microsomes in vitro, but
repeated consumption failed to do some in human subjects.3085 Likewise, both flurbiprofen1947 and
S-warfarin2316 metabolism were unaffected in humans.
10. Despite inhibiting the metabolism of CYP 2C9 drug substrates in vitro3112,3245 and in rats,3112 when 250
ml of pomegranate juice or a single 1 gram capsule of pomegranate extract with 689 mg
polyphenols was given in a crossover trial to 12 human subjects along with the substrate
positive control inhibitor fluconazole.3245
B.7.2.e Influence on CYP 2C19 Metabolic Conversion of Substrates

No Effect in Human Studies with Isoenzyme CYP 2C19 substrates ^
canadensis), and Oregon grape (Mahonia spp.) roots/barks − omeprazole3238
(Gb) Ginkgo leaf extract (Ginkgo biloba) – diazepam,2761 omeprazole,3091 ticlopidine,3227 voriconazole2679
[See Note 1.]
(La) English lavender flowers (Lavandula angustifolia) – omeprazole3303
Notes:
1. In a 12-day study with 18 healthy Chinese men, ginkgo standardized extract at 280 mg daily increased
metabolism of omeprazole and mephenytoin.2301,2302 HOWEVER, EGb 761 given at 120 mg twice
daily or 240 mg once daily for 8 days to 18 healthy Caucasian men and women caused no
significant effect in the metabolism of a single dose of omeprazole.3091 Also, in 12 healthy
Chinese men 240 mg ginkgo standardized extract daily for 8 weeks did not influence diazepam
metabolism by CYP2C19, responsible for 50-60% of its clearance.2761
B.7.2.f Influence on CYP 2D6 Metabolic Conversion of Substrates

Drugs: dextromethorphan – bb,3238 cc,2938 rs2970
metoprolol – sa2767
canadensis), and Oregon grape (Mahonia spp.) roots/barks
(Vaccinium spp.)
(sa) salvianolic acid B from dan shen roots (Salvia miltiorrhiza)
No Effect in Human Studies with Isoenzyme CYP 2D6 substrates p.426
(Gb) Ginkgo leaf extract (Ginkgo biloba) – debrisoquin,1328,1808,2302 dextromethorphan1840,3091
(La) English lavender flowers (Lavandula angustifolia) – dextromethorphan3303
(SJ) St John's wort herb (Hypericum perforatum) – [CORRECTION: debrisoquin superscript '1328'
should be deleted]
(Te) Tea (green) leaf catechin extract (Camellia sinensis) – dextromethorphan2810
Notes
2. [Note CORRECTION: an exception to no significant effect of St. John's wort on debrisoquin in human
studies is a 23% increased urinary recovery ratio of debrisoquin metabolite in one study,
indicative of possible Pgp induction.1328]
6. The study with 42 healthy humans showing significant inhibition of dextromethorphan metabolism
involved taking 1 gm of resveratrol orally once daily for 4 weeks.2970 Consumption of smaller
doses may not have this effect, and this 1 gm/day resveratrol dosage could not reasonably be
maintained for a month by eating the whole fruit of grapes, blueberries, and/or mulberries.
B.7.3 Specific Enzyme Influences of Herbal Agents on Phase II Conjugation p. 426
97
(Bold indicate human studies (subject criteria noted); organ sources of enzymes identified from in vitro
and animal studies)
B.7.3.a Influence on Activity and/or Content of Glutathione S-Transferases (GSTs)
Conjugation Inducers
(Am) Amla fruit (Emblica officinalis) – liver2853,2854
(Bp) Black raspberry fruit (Rubus occindentalis) – liver2460
(Br) Broccoli florets or sprouts [e water extract] (Brassica oleracea v. italica) – (e) bladder,3401 skin
(A1)2896
(cc) curcumin in turmeric root (Curcuma longa, Curcuma aromatica) – liver2783
(Chb) Chokeberry fruit [juice] (Aronia melanocarpa) – liver (A)3429
(Cl) Clove oil (Syzygium aromaticum) − liver, forestomach, small intestine2954
(Co) Coleus root (Coleus forskohlii) – liver3290
(eg) eugenol as in clove buds (Syzygium aromaticum) – liver2959
(Gb) Ginkgo leaves (Ginkgo biloba) – liver (P1)3226
(Li) Little ironwood herb (Vernonia cineraea) – liver2790
(os) organosulfides in garlic cloves (Allium sativum) – kidneys3140
(Sb) Shrubby basil leaf oil (Ocimum gratissimum = O. suave) – liver3014
(sr) sulforaphane from broccoli sprouts and tops (Brassica oleracea v. italica) – skin (A1)2896
(Tl) Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) – liver,3015,3364 skin3213
B.7.3.b Influence on Activity and/or Content of UDP-Glucuronosyl Transferases (UGTs)
Conjugation Inhibitors
(Cb) Cranberry fruit/juice (Vaccinium macrocarpon) – liver (1A9)3079
(cy) chrysin from passion flower leaves (Passiflora incarnata, Passiflora coerulea) – liver (1A1)3242
(ep) epigallocatechin gallate [EGCG] from green tea leaves (Camellia sinensis) – liver (1A1),3241
(1A4)3079
(Ep) Echinacea purpurea root (Echinacea purpurea) – liver (1A1)3241
(Gb) Ginkgo leaf extract (Ginkgo biloba) – liver (1A9), intestine (1A8,1A9)3191 [not liver (1A1)3190]
(kf) kaempferol as in tea (black and green) leaves (Camellia sinensis), kale leaves (Brassica oleracea v.
acephala ), etc. – liver (1A9), intestine (1A8,1A9)3191
(Mt) Milk thistle seeds (Silybum marianum) – liver (1A1),3241 (1A6, 1A9)3079
(Vaccinium macrocarpon), etc. – liver (1A9), intestine (1A8,1A9)3191
(Sp) Saw palmetto fruit (Serenoa repens) – liver (1A1),3241 (1A6)3079
(tn) tangeretin as in citrus fruit/juice (Citrus spp.) – liver (1A1)3242
(cc) curcumin in turmeric root (Curcuma longa, Curcuma aromatica) – colon, intestine3240
(cn) coumarin as in sweet clover (Melilotus officinalis), etc.
(Cr) Crucifers, specifically Brussels sprouts and/or cabbage (Brassica oleracea) –intestine, liver3240
(ea) ellagic acid as in strawberry leaves and seeds (Fragaria spp.), raspberry leaves and seeds (Rubus
spp.), black walnut leaves and nuts (Juglans nigra), etc. – liver3240
(eg) eugenol as in clove buds (Syzygium aromaticum) – liver2959
(Gb) Ginkgo leaf extract (Ginkgo biloba) – liver (1A1)3192
(go) ginkgolides A&B in ginkgo leaves (Ginkgo biloba) – liver (1A1)3192
(Vaccinium macrocarpon), etc. – intestine, liver3240
No effect in humans
(Ag) American ginseng root extract (Panax quinquefolius) – zidovudine2325
B.7.3.c Influence on NAD(P)H:Quinone Oxidoreductase 1 (Quinone Reductase [QR]) or DT-
Diaphorase Activity and/or Content
98
(8pn) 8-prenylnaringenin from hops strobiles (Humulus lupulus) – breast3457
(Ag) American ginseng root (Panax quinquefolius) – heart2928
(Bl) Blueberry fruit (Vaccinium spp.) − liver3261
(Br) Broccoli florets or sprouts [e water extract] (Brassica oleracea v. italica) – (e) oral,3534 skin,2895,2896
skin,2895,2896,3037 (e) bladder3401
(Chb) Chokeberry fruit [juice] (Aronia melanocarpa) – liver3429
(Hp) Hops strobiles (Humulus lupulus) − liver3457
(iq) isoliquiritigenin from licorice root (Glycyrrhiza glabra, G. uralensis), tonka bean seeds (Dipteryx
odorata, D.oppositifolia), etc. – liver2971
(sr) sulforaphane from broccoli sprouts and florets (Brassica oleracea v. italica) – mammary
epithelium,3400 skin,3037 skin, skin2895,2896
(tg) tigloylgomisin H lignan from schisandra fruit (Schisandra chinensis) – liver3139
(xh) xanthohumol and/or isoxanthohumol in hops strobiles (Humulus lupulus) – liver3457
B.7.3.f Influence on Activity of Estrogen Sulfotransferases (SULT1E1) NEW

(By) Blueberry fruit juice (Vaccinium corymbosum) – colon3427
(Chb) Chokeberry fruit juice (Aronia melanocarpa) – colon3427
(Cof) Coffee roasted seed infusion (Caffea arabica) – colon3427
(Pm) Peppermint leaf infusion (Mentha piperita) – colon3427
B.7.4 Specific Enzyme Influences of Herbal Agents on Steroid Metabolism p. 433

(Bold abbreviations indicate human studies with subject criteria noted; organ enzyme sources identified
for in vitro tissue studies [non-italicized] and animal studies [italicized])
B.7.4.a Aromatase (CYP 19) Conversion of Androstenedione to Estrone and Testosterone to
17beta-Estradiol
Conversion Inhibitors
(bA) biochanin A from red clover leaves, flowers (Trifolium pratense), etc. − breast3393
(Dm) Damiana leaves (Turnera diffusa) − liver3231
canadensis), and Oregon grape (Mahonia spp.) roots/barks − breast3393
(ep) epigallocatechin gallate [EGCG] from green tea leaves (Camellia sinensis) – cervix3393
(Gw) Grape red wine (Vitis vinifera) – systemic3175
(iq) isoliquiritigenin from licorice root (Glycyrrhiza glabra, G. uralensis), tonka bean seeds (Dipteryx
odorata, D.oppositifolia), etc. – breast3393
(is) isoflavone [genistein] in soy beans (Glycine max) − liver3393
(ms) -mangostin in mangosteen (Garcinia mangostana) pericarp − breast3393
(thc) tetrahydrocannabinol in cannabis (Cannabis sativa) − breast3393
(Wb) White button mushroom (Agaricus bisporus) – breast, breast3458
B.7.4.b 5alpha-Reductase Conversion of Testosterone to Dihydrotestosterone
(Am) Amla fruit (Phyllanthus emblica) – liver3491
(Ft) Foti root [emodin3367] (Polygonum multiflorum) – prostate,3367 epididymis3490
(Gg) Greater galangal rhizomes (Alpinia galanga) – liver3491
(gp) gossypol in cotton root bark (Gossypium herbaceum, G. hirsutum) – prostate (types 1 & 2)3495
(Gr) Ginger rhizomes (Zingiber officinale) – liver3491
(gs) ginsenosides [Ro, Rd] (Panax ginseng) – epididymis, hair follicle3489
(Gs) Asian ginseng rhizomes/ root (Panax ginseng) – epididymis, hair follicle3489
(Hg) Horny goat weed leaf (Epimedium grandiflorum) – epididymus3490
99
(is) isoflavones as in soy beans (Glycine max), red clover flowers (Trifolium pratense), etc. – prostate
(type 2)3495
(Jg) Japanese ginseng rhizomes (Panax japonicus) – epididymis3489
(kf) kaempferol as in tea (black and green) leaves (Camellia sinensis), kale leaves (Brassica oleracea v.
acephala ), etc. – prostate (type 2)3495
(Kz) Kudzu flower (Pueraria thomsonii) – epididymis, hair follicle3490
(Lg) Lesser galangal rhizomes [diarylheptanoids] (Alpinia officinarum) – prostate3494
(Ls) Lemongrass herb (Cymbopogon citratus) – liver3491
(na) nordihydroguaiaretic acid in chaparral *(Larrea tridentata) – prostate (types 1 & 2)3495
(Oy) Oyster mushroom (Pleurotus ostreatus) – liver (type 1), prostate (type 2)3492
(Rs) Reishi mushrooms (Ganoderma lucidum) – prostate, prostate (type 2), liver (type 1)3492
(Sf) Saffron pistil (Crocus sativus) – epididymis3490
(Sh) Shiitake mushroom (Lentinula edodes) – liver (type 1), prostate (type 2)3492
(Sw) Safflower flowers (Carthamus tinctorius) – liver, hair follicle3491
B.7.4.d 11beta-Hydroxysteroid Dehydrogenase type 1 or 2 Conversion of Cortisol to Cortisone
(gl) glycyrrhetinic acid/glycyrrhizin from licorice root *(Glycyrrhiza glabra, Glycyrrhiza uralensis) – (t1,
t2) liver,559,3455 (t2) kidney,3022
(Li) Licorice root *(Glycyrrhiza glabra) – in Addison's disease3021
B.7.4.g 17beta-Hydroxysteroid Dehydrogenase type 1 Conversion of Estrone to Estradiol
(Bl) Blueberry fruit (Vaccinium corymbosum) – mammary3082
(By) Black raspberry fruit (Rubus occidentalis) – mammary3082
(ea) ellagic acid as in strawberry leaves and seeds (Fragaria spp.), raspberry seeds and leaves (Rubus
spp.), black walnut leaves and nuts (Juglans nigra), etc. – mammary3082
B.7.4.i 11beta-Hydroxysteroid Dehydrogenase type 1 Conversion of Cortisone to Cortisol
(gl) glycyrrhetinic acid/glycyrrhizin from licorice root *(Glycyrrhiza glabra) – liver3022
B.7.4.j Sterol 27-Hydroxylase (CYP27A1) Conversion of Cholesterol to Bile Acids
and Bioactivation of Vitamin D3
Conversion Inducers
(bb) berberine from barberry bark (Berberis vulgaris), coptis (Coptis spp.), goldenseal *(Hydrastis
canadensis), and Oregon grape root bark (Mahonia aquifolium), etc. − liver2933
100
Appendix C
HERBALS CONTRAINDICATED FOR MOTHERS AND CHILDREN
C.1 During Pregnancy p. 439
Substances that interfere with the mother’s hormonal balance or fetal genetic expression
can disrupt fetal development. In the cases of the gender-specific reproductive organs, plants
shown in humans or animals to cause gonadotropic or sex hormone (H) changes may alter
normal expression. Mutagens (M) and genotoxins (G) may likewise disturb normal growth as
shown by in vitro studies. Teratogens (T) have been shown to interfere with normal
development of particular structures, and plants with fetotoxins (F) endanger the essential
functions of the developing child. In cases where such substances cause these effects to occur in
utero, birth defects are a possible outcome that otherwise could be avoided.
(Based in part on reference 2791, 3056-3058, 3377, 3496.)
American mistletoe leaves, stems *(Phoradendron macrophyllum) A
Bitter melon fruit /seeds (Momordica charantia) A; T
California mugwort herb (Artemisia douglasiana) A
Feverfew herb (Tanacetum parthenium) H
Horsetail herb (Equisetum spp.) A
Pennyroyal (See: American pennyroyal, European pennyroyal) E, A
Saw palmetto fruit (Serenoa repens) H
Wormwood tops, leaves *(Artemisia absinthium) H
Yerba mansa (Anemopsis californica) A
C.2 While Breast Feeding

Some herbal preparations are given safely as galactogogues to increase milk production,
For example, micronized silymarin given to 25 women with borderline levels of lactation
significantly increased milk production after 30 and 63 days compared to placebo. No evidence
of silymarin was found in the breast milk of 5 women after 5 days.2898 This micronized
standardized silymarin extract was shown after 14 days in female rats to increase prolactin levels
that remained significantly elevated another 66 days, likely involving dopamine D 2 receptors.2967
A granular herbal tea formula containing fenugreek was also shown to significantly enhance
milk production of a group of 22 mothers, compared to placebo apple tea granules in 22 new
mothers or no intervention in 22 others, during the first week of life for their newborns. No
maternal or neonatal adverse effects were reported.2899 The fenugreek formula also contained
among other herbs goat's rue, fennel, and fennel essential oil, the latter made up almost entirely
of the estrogenic component anethole.14 However, in a report of 2 cases of mothers consuming
more than 2 liters daily of herbal tea mixtures with extracts of goat's rue, fennel, licorice, and
anise for 15-20 days after birth, the breast-fed infants failed to thrive and showed nervous system
symptoms after the first week. When the teas were stopped, the infants recovered and did
well.1141 Some active constituents of medicinal plants can be excreted in breast milk intact or as
metabolites that maintain much of the activity of the original compounds, and problems are more
likely when large quantities of the herbal extracts are consumed for extended periods.
Infants under 6 months of age should optimally be given only breast milk and not be
given herbal teas or other extracts or medicinal preparations unless prescribed by a recognized
health expert. Giving even safe herbal teas to an infant can reduce its milk consumption and vital
nutrient intake. As regards a nursing mothers consuming unnecessary herbal products, unless the
specific intent is to treat the child by this means, it is preferable to not expose the breast feeding
101
infant to potent medicinal compounds. Especially when particular plant compounds are known to
inadvertently produce their unintended pharmacologic effect in the nursing child, caution should
be used in taking herbals that contain these.
102
Appendix D
VITAMIN/MINERA/DRUG INTERACTIONS
D.1 Drug and Mineral Interactions with Vitamin Supplements p. 457
Interference between vitamins and drugs or prescription mineral supplements can work
both ways. In some cases drugs will lower vitamin (LV) oral absorption and/or serum levels or
increase excretion or metabolism, while in other cases medications can raise vitamin (RV)
bioavailability or increase their effects. In cases where drugs reduce vitamin levels, consumption
of plant sources of the vitamin would be highly desirable. Vitamins may also raise drug (RD) or
mineral (RM) serum levels or increase their effects, or they may lower drug (LD) or mineral
(LM) levels or reduce their effects. Vitamin/drug or vitamin/mineral interactions listed below
have caused either toxicity (t) or insufficient (i) effects for one or the other. Clinical findings
for humans are emphasized in bold. Other interactions listed have produced observable
changes without clinically-apparent adverse effects, but monitoring is advisable.
References: 3243, 3278
D.1.6 Vitamin B12 (Cyanocobalamine) / Drug Interactions
p. 462
Esomeprazole - LV
Lansoprazole - LV
Omeprazole - LV
Pantoprazole - LV
Rabeprazole - LV
D.1.8 Vitamin C (Ascorbic Acid, Ascorbates) / Drug Interactions
p. 464
Esomeprazole - LV
Lansoprazole - LV
Omeprazole - LV
Pantoprazole - LV
Rabeprazole - LV
D.1.9 Vitamin D (Calciferol) / Drug Interactions p. 465
Efavirenz - LVi
D.2 Drug and Vitamin Interactions with Mineral Supplements p. 467

Interference between minerals administered orally together with drugs or prescription
vitamin or mineral supplements can work both ways. In some cases drugs will lower mineral
(LM) oral absorption and/or serum levels or increase their excretion, while in other cases
medications can raise mineral (RM) bioavailability or increase their effects. The mineral forms
listed below are those that have most commonly been shown to interact with the drugs. In cases
where drugs affect the mineral levels, they usually act independently of the form of the mineral
consumed, affecting dietary as well as supplementary sources. Adverse interactions are noted by
emphasizing the drug in bold if documented in human studies.
References: 2823,3278
D.2.1 Calcium (as Carbonate) / Drug Interactions p. 470
Esomeprazole - LM
Lansoprazole - LM
Omeprazole - LM
Pantoprazole - LM
Rabeprazole - LM
103
D.2.4 Iron (as Ferrous Sulfate) / Drug Interactions p. 474
Esomeprazole - LM
Lansoprazole - LM
Omeprazole - LM
Pantoprazole - LM
Rabeprazole - LM
D.2.5 Magnesium (as Oxide) / Drug Interactions p. 476
Bumetanide - LM
Dexlansoprazole - LM
Esomeprazole - LM
Indapamide - LM
Lansoprazole - LM
Metolazone - LM
Omeprazole - LM
Pantoprazole - LM
Rabeprazole - LM
Torsemide - LM
104
Appendix E
HERBALS AS POTENTIAL COMPLEMENTARY ADJUNCTS
WITH MEDICINES
[Note CORRECTION: In Appendices B and E in the first l00 copies of the book, asterisks (*) are
missing in front of the scientific Latin names for a number of listed herbs designated with * in the
main body of the text as containing potentially toxic compounds. (European pennyroyal herb
*(Mentha pulegium) near the top of page 366 lacks an asterisk in these books.) In Appendix E the
other herbs that may be missing the * include: Black cohosh, Bryonia, Cannabis, Cayenne,
Chinese rhubarb, Cinchona, Garlic, Goldenseal, Jamaica dogwood, Licorice, Sage, Thuja,
Thunder god vine, Valerian, and Wormwood.]
E.1 Potentially Beneficial Combinations of Herbals with Drugs

E.1.1 Herbs and Those Drugs Which May Potentially Be Complemented p. 484
Amla fruit (Emblica officinalis) – isoniazid, pyrazinamide, rifampicin,2857,2858 cyclophosphamide,2853,2955
cisplatin,2860 doxorubicin2859,2860
American ginseng (Panax quinquefolius) root – ACE inhibitors, beta-blockers, calcium channel
blockers,3420 chemotherapy,2916,3293 influenza vaccine,2918,2919 cyclophosphamide,2924,2925
mitomycin C,2922 N-acetyl cysteine, vitamin C 2923
berry − 5-fluorouracil2927
Arjuna bark (Terminalia arjuna) – isosorbide dinitrate2661,3286
Arnica flowers *(Arnica montana) ‒ acetaminophen,2805 hydroxyethyl salicylate3090
Ashwagandha (Withania somnifera) root − adriamycin, cyclophosphamide, epirubicin,3252
ethambutol,3233 5-fluorouracil,3252 isoniazid, pyrazinamide, rifampicin,3233 SSRI's,3548
taxotere,3252 gentamicin3253
Asian ginseng root (Panax ginseng) – donepezil, galantamine, memantine, rivastigmine,3059
cyclosporine,3522 cisplatin2725
Astragalus root (Astragalus membranaceus) – enalapril2728
Barberry root bark (Berberis vulgaris) – simvastatin,2905 amphotericin B,3107 doxorubicin,3148
stanols2932,2933
Bilberry fruit (Vaccinium myrtillus) – latanoprost,2966 doxorubicin3514,3515
Black cumin seed (Nigella sativa) – beclomethasone, beta-agonists,2988 corticosteroids,2988,2989
diclofenac,3114 fluticasone,2988 folic acid, hydroxychloroquine, methotrexate,3114
omeprazole,3312 theophylline,2988 acetaminophen,2983 doxorubicin,2430 gemcitabine,2985
gentamicin,3259 ifosfamide,2431 oxaliplatin2985
Black pepper fruit (Piper nigrum) – calcium,3471 EGCG,2935 emodin,3459 iron, zinc3471
Burdock root (Arctium lappa) – acetaminophen, glucosamine,3539 acetic acid, alcohol (ethanol)3541
Calamus rhizome (Acorus calamus) − vincristine3375
Cannabis tops *(Cannabis sativa) – anticholinergics,2751 anticonvulsants, antidepressants,2940
baclofen,3305 codeine, dextropropoxyphene, dihydrocodeine,2748 glatiramer, interferon beta-
1a,b,3305 methadone,2748 methotrexate,2942 morphine,2748,3126 NSAIDs,2940 oxycodone,2748,3126
pethidine,2748 tizanidine,3305 tramadol2748
Cat’s claw bark (Uncaria tomentosa) – doxorubicin3331
Cayenne fruit (Capsicum frutescens) − calcium, iron, zinc3471
Chaga mushroom (Inonotus obliquus) − cyclophosphamide3504
Chamomile flowers (Matricaria recutita) – cisplatin3374
Chokeberry fruit (Aronia melanocarpa) – amiodarone,3436
Clove buds (Syzygium aromaticum) − indomethacin2957
105
Cocoa seeds (Theobroma cacao) – ACE inhibitors,3077 angiotensin receptor blockers,3077
antihypertensives,2740 beta-blockers,3077 diuretics,3077 metformin,2740 oral anticoagulants,3077
statins2740,3077
Cola (Cola nitida) seed – ciprofloxacin, perfloxacin, levofloxacin3034
Coptis root (Coptis spp.) – simvastatin,2905 amphotericin B,3107 doxorubicin,3148 stanols2932,2933
Corn silk/stigma (Zea mays) − gentamicin,3486 camptothecin, cisplatin, etoposide, 5-fluorouracil3488
Cranberry fruit [CORRECTION: NOT leaves] (Vaccinium macrocarpon) – oral hypoglycemics,3098
doxorubicin3080
Crucifers tops, leaves, sprouts (Brassica spp.) − cisplatin,2934 trabectidin2177
Dog rose hips (Rosa canina) − acetaminophen, chloroquin, leflunomide, methotrexate, NSAIDs,
steroids2962
Dong quai root (Angelica sinensis) – tamoxifen,3517 enalapril2728
Echinacea angustifolia root (Echinacea angustifolia) − influenza vaccine3178
Echinacea pallida whole plant (Echinacea pallida) – cisplatin2726
English lavender (Lavandula officinalis) – diclofenac3533
English plantain leaves (Plantago lanceolata) ‒ indomethacin2838
Evening primrose seed (Oenothera biennis) – isotretinoin3478
Fenugreek seeds (Trigonella foenum-graecum) – ibuprofen,3416 L-dopa,3394 mefenamic acid,
NSAIDs3416
Frankincense gum resin (Boswellia serrata) – beclomethasone, budesonide, fluticasone, formoterol,3542
ibuprofen,2483,2804 metformin,3413 sameterol3542
French maritime pine bark (Pinus pinaster) – albuterol,3094 chlorambucil,3333 fluticasone,3093
latanoprost,2966 mitoxantrone, prednisolone,3333 salbutamol,3093 zafirlukast3094
Garlic fresh cut clove [# = aged garlic extract] *(Allium sativum) – #ACE inhibitors, #angiotensin II
receptor antagonists,2757 atorvastatin,3313 #beta-blockers,2757 #calcium channel blockers,2757
chorhexidine,2711 #diuretics,2757 ethambutol, isoniazid, pyrazinamide, rifampicin,3169
captopril,2756,3518 isoproterenol,3518 gentamicin3387
Ginger root (Zingiber officinale) ‒ acetaminophen,3314,3316 cisplatin,2909 cyclophosphamide,3092,3537
dexamethasone,2909,3092 docetaxel,3092,3537 doxorubicin,2909,3537 epirubicin,3092 5-flouracil,3537
granisetron,3092 ondansetron,2909 oral hypoglycemics,3501 acetaminophen,3473,3474,3475
atorvastatin,2849 calcium,3471 iron,3471 morphine,3321 zinc3471
Ginkgo leaves (Ginkgo biloba) – adapalene,3499 donepezil, galantamine,3484 olanzapine,3291
radioiodine,3095,3096 rivastigmine,3484 cisplatin,3373 dexamethasone,3147 gentamicin,3260
isoproterenol3185
Goldenseal roots/rhizome *(Hydrastis canadensis) – simvastatin,2905 amphotericin B,3107 doxorubicin,3148
stanols2932,2933
Guarana seeds (Paullinia cupana) – cyclophosphamide, doxorubicin, fluorouracil2920
Hawthorn leaves/flowers (Crataegus spp.) – cyclophosphamide3344
Hops strobiles (Humulus lupulus) − benzodiazepines2634
Kudzu root (Pueraria thunbergiana = P. lobata) – cisplatin2724
Kutaki root (Picrorhiza kurroa) – acetaminophen,3160 chloroquine,2937 ethinylestradiol,3160rifampicin3161
Larch bark (Larix spp.) – pneumococcal vaccine,2739 tetanus vaccine3351
Licorice root/rhizome *(Glycyrrhiza glabra, G. uralensis) – indomethacin2976
Long pepper fruit (Piper longum) − calcium,3471 EGCG,2935 iron, zinc3471
Lycium (= Goji) berry (Lycium barbarum) − doxorubicin,3029,3110 mitomycin C3030
Maca root (Lepidium meyenii) – SNRI, SSRIs, venlafaxine3483
Maitake mushroom (Grifola frondosa) – clomiphene citrate,2910 adriamycin, cisplatin, 5-
fluorouracil3341
Milk thistle seeds (Silybum marianum) – glibenclamide, metformin,3479 acetaminophen2824,3181
Olive fruit oil (Olea europaea) – antibiotics,3500 atenolol, doxazosin, hydrochlorothiazide, lisinopril,
nifedipine1773
106
Oregon grape root bark (Mahonia spp.) – simvastatin,2905 amphotericin B,3107 doxorubicin,3148
stanols2932,2933
Passion flower herb (Passiflora incarnata) − benzodiazepines2634
Pelargonium root (Pelargonium sidoides) − augmentin, budesonide, fenoterol, ipratropiumbromide,
ofloxacin, salmeterol3269
Peppermint leaves (Mentha x piperita) – granistron, dexamethasone, metoclopramide3285
Pomegranate fruit (Punica granatum) − hydroxychloroquine, methotrexate, prednisone, NSAIDs,
sulfazine,3024 docetaxel3381
Quassia (Surinam) bark (Quassia amara) – hydrochoric acid,3384 indomethacin3382-3384
Saffron stigmas (Crocus sativa) – dorzolamide,3437 fluoxetine,3480,3481 timolol3437
Sage leaves *(Salvia officinalis) – vincristine3372
Sanchi ginseng root/rhizome (Panax notoginseng) − aspirin,3076 diclofenac, leflunomide, prednisone3418
Saw palmetto fruit (Serenoa repens) − prulifloxacin,3414 tamsulosin3411
Shiitake mycelia Lentinula edodes (= Lentinus edodes) – cyclophosphamide, epirubicin,3502 5-
fluorouracil,3502,3503 folate,3502 irinotecan,3502,3503 levofolinate, mitomycin C, taxol,3503 TS-1,3502
UFT3502,3503
Soy beans (Glycine max) – adriamycin, carboplatin, cisplatin, cyclophosphamide, dacarbazine,
etoposide, fenofibrate,3510 ifosfamide, irinotecan, paclitaxel, procarbazine, temozolamide,
vincristine2813
St. John's wort herb (Hypericum perforatum) − indomethacin, sodium valproate3248
Stinging nettle leaves (Urtica spp.) – acetaminophen [paracetemol] aspirin, celecoxib, diclofenac,
ibuprofen, ketoprofen, naproxen, opiates, piroxicam, sulindac, tenoxicam2722
root – nicotine3456
Sweet annie herb (Artemisia annua) – curcumin2914
Sweet cherries (Prunus avium) – allopurinol, colchicine3299
Tart cherry fruit (Prunus cerasus) − allopurinol, celecoxib, indomethacin,3298,3302 sulindac,2432
atorvastatin3145
Tea [green] leaves (Camellia sinensis) – ciprofloxacin,3038 indomethacin2752
Tea tree leaf oil (Melaleuca alternifolia) − diclofenac, minoxidil3371
Thunder god vine peeled root *(Tripterygium wilfordii) – auranofin,3281 methotrexate,3280-3282
NSAIDs,3281 sulfasalazine3282
Tibetan rhodiola (Rhodiola crenuata) − antihistamines, corticosteroids, LABA, LAMA,
SAMA+SABA, xanthines3508
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) − acetaminophen,3181 acetic acid, aspirin,3218
isoproterenol,3185,3239 meloxicam,3183 radioiodine,3184,3186 vincristine,3179 cyproterone acetate3196
Turmeric root (Curcuma longa, C. aromatica) – acetaminophen,2802,3247 analgesics,3415 antiherpetics,
antitoxoplasmic drugs,2803 carboplatin,3485 CCNU,3363 celecoxib,2802 cisplatin,3363,3407,3485
cyclophosphamide,3407 cycloplegics,2803 diclofenac,3103 docetaxel,3407 etoposide,3407 5-
fluorouracil,3363,3407 fluoxetine,3348 gemicitabine,3363 immune suppressants,2803 isoniazid,2995
methotrexate,3407 MOPP/ABVD/COPP,3363 mydriatics,2803 naproxen,3433 NSAIDs,2721,2803,3415
oral hypoglycemics,3097 pyrazinamide, rifampicin,2995 steroids,2803 taxol,3485 topotecan,3407
vinblastine,3363 arteether,2914 cisplatin,2877 clarithromycin,3516 docetaxel,3319 gemcitabine,3118
paclitaxel,2781,3117 artemisinin2914
Valerian root (Valeriana officinalis) − benzodiazepines2634
E.2 Herbal Aids for Modifying Substance Abuse p. 489

Studying cannabis use for withdrawal symptoms by opiate or other hard-drug addicts or
alcoholics may be a reasonable subject for controlled research, since the benefits of overcoming
these self-destructive addictions outweighs the limited risks of short-term marijuana use.3545 One
potential adverse effect associated with use of cannabis by addicted individuals outside of rarely-
107
approved clinical studies includes the legal consequences, even though some states that have
approved its limited medical use. Ironically, the deterrence associated with concern for its federal
illegal status may be more prevalent among those who would want to utilize it therapeutically
than those who simply exploit it recreationally. On the other hand, concurrent use of cannabis
with opiates or alcohol results in additive effects and enhanced impairment.1076,1077 Therefore,
though cannabis has been used successfully to some extent to help reduce opioid or alcohol
dependence,3270,3545 personal use of cannabis to reduce alcohol intake should not be considered
an appropriate rationale, since concurrent abuse of both together not unusual.628
Simply substituting one form of drug dependence for another necessarily fails to address
the underlying cause(s).
E.2.1 The drugs whose dependence or adverse effects may potentially be alleviated by certain
herbs or their derivatives include alcohol (Alc), amphetamines (Amp), benzodiazepines (Bzd),
cocaine (Coc), nicotine (Nic), and opiates (Opi). Herbal facilitators of acute withdrawal or
beyond may function pharmacologically as mild anxiolytics (X), sedatives (S), relaxants (R)
for muscle tension and cramps, or antidepressants (D). These types of herbal agents have been
shown in animal or human studies to impact dopamine pathways, improve sleep, diminish pain,
and/or in other ways help make the withdrawal process less uncomfortable. Herbal extracts or
isolated components may bind to receptor sites of the drug or alter its enzymatic conversions
in vitro (V). Reports of animal studies (A), empirical reports (E), or human studies (H)
document that some herbal agents facilitate specific drug withdrawal or reduce its adverse
effects. The studies may involve the powdered herb (h), its extracts (e), or a component (c) or a
combination (C) of several herbal preparations.
Scientific human withdrawal trials are indicated in bold for emphasis. Negative studies are
in brackets; counterproductive results are indicated by "not." Reduction of drug adverse
effects only is indicated by closure within parentheses. In regards to alcohol dependence,
some herbal preparations provide amelioration of some of ethanol's adverse effects such as
stomach damage (sd) [ulceration] and liver damage (ld).
E.2.1 Botanical Adjuncts for Reducing Recreational Drug Use and/or Damage
American ginseng root (Panax quinquefolius) – Amp: Ac2929
Coc: (Ac2931)
Amla fruit (Emblica officinalis) – Alc: (ld Ae,2856,3152 Ac3153,3154,3155)
Apricot fruit (Prunus armeniaca) – Alc: (ld Ah3157)
Ashwagandha root (Withania somnifera) – Opi: Ae3466
Asian ginseng root (Panax ginseng) – Amp: Ac2929,2930
Coc: Ac2931
Barberry bark (Berberis vulgaris) − Coc: Ac2753
Belleric myrobalan fruit (Terminalia bellirica) − Alc: (sd Ae3168)
Bishop's weed fruit (Trachyspermum ammi syn. T. copticum) – Opi: Ae3461
Black cumin seed (Nigella sativa) – Alc: (sd Ae,2984 Ac2987)
Opi: Hh2982
Black pepper fruit (Piper nigrum) – Alc: (sd Ah, Ac3347)
Black raspberry fruit/seeds (Rubus occidentalis) – Alc: (ld Ac3153,3154,3155)
Blackberry fruit/seeds (Rubus spp.) – Alc: (ld Ac3153,3154,3155)
Borage seed (Borago officinalis) − Alc: Af3234
Burdock root (Arctium lappa) – Alc: (ld Ae3158)
Cannabis tops *(Cannabis sativa) – Amp: Ac2977
Coc: Ac2977
Opi: Ac2973
108
Chaparral leaves (Larrea tridentata) − Alc: (sd Ac3246)
Chili fruit *(Capsicum annuum) – Alc: (sd Ah, Ac3347)
Chinese raisin tree fruit (Hovenia dulcis) – Alc: Ae (ld Eh)2845
Chinese skullcap root (Scutellaria baicalensis) – Alc: (ld Ae2839)
Clove buds (Syzygium aromaticum) − Alc: (sd c2958)
Coptis rhizome (Coptis chinensis) − Coc: Ae,c2753
Coriander fruit (Coriandrum sativum) – Alc: (sd Ah3264)
Fenugreek seeds (Trigonella foenum-graecum) – Alc: (ld Ae3156)
Garlic bulbs *(Allium sativum) – Alc: (ld Ah,3166 Ae,f3149)
Ginger rhizome (Zingiber officinale) – Alc: (sd Ah, Ac3347)
Goldenseal roots/rhizome *(Hydrastis canadensis) − Coc: Ac2753
Grape red wine (Vitis vinifera) − Alc: Ae,3162 Ac3163,3164 [not Ac3165]
Hawthorn berries (Crataegus laevigata, C. monogyna) − Alc: (sd Ae3343)
Jambolan seeds (Syzygium cumini) − Alc: (ld Ae3167)
Kudzu root (Pueraria lobata) – Alc: Ac,3283 He,3509 Hc3221
Kutaki root (Picrorhiza kurroa) – Alc: (ld Ae2936)
Lemon balm herb (Melissa officinalis) – Opi: Ae3461
Little ironweed herb (Vernonia cinerea) – Nic: He2713
Lobelia herb *(Lobelia inflata) – Amp: Ac3439, 3440, 3441
Nic: Hc3453,3454
Milk thistle seeds (Silybum marianum) – Alc: (ld Ae3156,3283)
Oregon grape bark (Mahonia aquifolium) − Coc: Ac2753
Passion flower leaves (Passiflora incarnata) – Se2879
Peppermint herb (Mentha piperita) – Opi: Ae3461
Pomegranate fruit/seeds (Punica granatum) – Alc: (ld Ac3153,3154,3155)
Prickly pear pads (Opuntia spp.) – Alc: (sd Ah3505)
Quassia (Surinam) bark (Quassia amara) – Alc: (sd Ae3383,3384)
Raspberry fruit/seeds, leaves (Rubus idaeus) – Alc: (ld Ac3153,3154,3155)
Rhodiola root (Rhodiola rosea) – Nic: Ae3317
Rosemary herb (Rosmarinus officinalis) − Opi: Ae3464
Saffron stigma (Crocus sativus) − Opi: Ae3465
Scotch broom tops (Cytisus scoparius) – Nic: Hc3405
Shrubby basil leaves (Ocimum gratissimum = O. suave) − Alc: (sd e2953)
St. John’s wort herb (Hypericum perforatum) – Nic: [He2797,3378,3379]
Opi: Ae3462
Strawberry fruit/seeds, leaves (Fragaria spp.) – Alc: (ld Ac3153,3154,3155)
Summer savory herb (Satureja hortensis) – Opi: Ae3461
Tea black leaves (Camellia sinensis) – Alc: (ld Ae3150,3151)
green leaves – Alc: (ld Ae,c3149)
Opi: Xc, Ac3397
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) − Alc: (sd Ae3218)
Amp: (Ae3220)
Turmeric rhizome (Curcuma longa) – Alc: Ac,3395 (ld Ac1832,3159)
Valerian root *(Valeriana officinalis) – Opi: Ae3461
Winter melon fruit (Benincasa hispida) − Opi: Aj3463
E.3 Complementing Treatment of Inflammations p. 492

E.3.1-3.5 Drug treatments have advantages and drawbacks that differ, depending on the
type of drug. Drugs considered here in interactions with herbs are grouped as
corticosteroids (cortisone, dexamethasone, hydrocortisone, prednisone), NSAIDs (acemetacin,
109
aspirin, celecoxib, diclofenac, ibuprofen, indomethacin, ketoprofen, metamizol, naproxen,
piroxicam, phenylbutazone, rofecoxib, salicylates), and analgesics (acetaminophen
[paracetamol], codeine, morphine, propoxyphene HCl, propyphenazone, tramadol).
Herbs (h) and their extracts (e), fractions (f), and components (c) or smoke (s) are
considered here as anti-inflammatory and analgesic adjuvants when they enhance the clinical
effects of these drugs, reduce their adverse effects, or reduce their use (frequency or dose) by
humans (in bold) or in animals (italicized). Some botanical derivatives or components produce
additional anti-inflammatory and/or analgesic effects if used with drugs when applied topically
(t).
E.3.1 Enhancing the Effects of Corticosteroids p. 493

Black cumin seed (Nigella sativa) – e2988,2989
Frankincense resin extract (Boswellia serrata) – e2846
E.3.2 Enhancing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) p. 493
Black cumin seed (Nigella sativa) – f 3114
Fenugreek seed (Trigonella foenum-graecum) − h3416

Frankincense resin (Boswellia serrata) resin – e2804
French maritime pine bark (Pinus pinaster) – f2795
Purple passion fruit peel (Passiflora edulis) − e2951
Stinging nettle leaves (Urtica dioica) – h2722
Turmeric root [curcumin] (Curcuma longa, C. aromatica) – c2721,2802,3103,3433
E.3.3 Enhancing Outcomes When Using Analgesics p. 494
Arnica flowers (Arnica montana) ‒ te2805
Cannabis leaves/tops *(Cannabis sativa) – e,2748,2749 s2745,2750
Ginger root/rhizome (Zingiber officinale) – e3321
Stinging nettle leaves (Urtica dioica) – h2722
Turmeric root [curcumin] (Curcuma longa, C. aromatica) – c,2802 f3247
E.3.4 Protecting Against NSAID-induced Ulcers p. 494
Chaparral leaves (Larrea tridentata) − c 3246
Clove oil [eugenol] (Syzygium aromaticum) − c2957

Coconut milk (Cocos nucifera) − e3391
Coriander seeds (Coriandrum sativum) − h3264
English plantain leaves (Plantago lanceolata) ‒ e2838
Licorice root (Glycyrrhiza glabra) – e2976
Sea buckthorn fruit (Hippophae rhamnoides) – e1959
Shrubby basil leaves (Ocimum gratissimum = O. suave) − e2953
Tea leaves (Camellia sinensis) – e,f2752
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) − e3183,3218
E.3.5 Protecting Against Acetaminophen-induced Liver Toxicity p. 494
Black cumin seed (Nigella sativa) – c 2983
Garlic cloves (Allium sativum) – e3386

Ginger rhizome (Zingiber officinale) − h,3475 e3473,3474
Korean acanthopanax root bark (Acanthopanax koreanum) – c2727
Kutaki rhizome/roots (Picrorhiza kurroa) − f3160
Milk thistle fruit (Silybum marianum) – f2824,3181
Schisandra fruit (Schisandra chinensis) − c696
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) − e3181
E.4 Enhancing Chemotherapy and Chemoprevention
110
or Reducing the Adverse Effects p. 494
A systematic review of studies implicating risks of herb and food supplement interactions with
cancer drugs found 5 acceptable papers that surveyed a total of 806 cancer patients, of which 433
(53.7%) were combining supplements and drugs. Of these, 167 potential risks were identified in
60 patients (13.9%), but the risks were mainly theoretical and unsupported by clinical data. None
of the studies reported any actual adverse events that were associated with the combinations.3497
Much of the research thus far has been done on an isolated phytochemical component [c] or
components [cs]. When only isolated components are shown to enhance outcomes with
chemotherapy drugs by the research cited in this appendix section, especially with in vitro
studies, they often are not discussed with the associated herb(s) in the main body of this text.
E.4.1 & E.4.2 To differentiate the types of in vivo studies, human cases are in bold and studies
in animals are italicized, while the in vitro tests on cells are in regular type-face. Herbal
preparations used in the studies are noted in parentheses as a combination (C), the powdered
herb (h), its pyrogenic smoke (s), a complex solvent extract (e), an extract fraction (f) or an
isolated component [c] or components [cs]. Extracts may be further designated as aqueous
(ea), ethanolic (ee), or methanolic (em), etc. The main component (and chemopreventive
preparations in E.4.4) is named in brackets [component name] with the herb or identified by
abbreviation [c] with the drug, while abbreviations of other derivatives are named in the
parentheses (e.g., f for fraction) with the interacting drug.
E.4.3 ATP-binding cassette (ABC) transporter family is greatly involved with resistance to
chemotherapy. Efflux pumps P-glycoprotein (Pgp, or ABCB1) encoded by multridrug
resistance gene (MDR1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and
MRP-2, or ABCC1 and ABCC2), and breast cancer resistance protein (BCRP, or ABCG2)
are active in removing drugs or their conjugates from tumor cells back into the blood. The
inhibition of MDR1, MRP-1 and –2, and/or BCRP activity or their gene expression will
enhance the retention of chemotherapy drugs. The retention of antitumor drugs may also be
enhanced through inhibition of some subtypes of high-affinity glutamate transporters such as
GLAST and GLT-1. The tissue(s) and/or efflux protein(s) are listed along with the drugs that
have been shown to be impacted. The effect on chemotherapeutic agents has been demonstrated
mostly with isolated components in cell cultures in vitro, so the components are identified [in
brackets], usually a polyphenolic component (pc) or amino acid (aa).
E.4.4 The abbreviation for the preparation tested, as in E.4.1 & E.4.2, in combination with the
chemopreventive drug is followed by the specific type of cancer or precancerous lesion that they
have been shown to synergistically reduce. The abbreviation for the preparation tested in
combination with the chemopreventive drug is followed by the specific type of cancer or
precancerous lesion that they have been shown to synergistically reduce. The types of
preparations listed in brackets between the common and scientific names of the botanicals are
those forms of the botanical that have been shown by themselves to inhibit some cancer(s) in
humans (cancer types in bold) or in animals, or various cancerous cell cultures or process(es) in
vitro, for which reference citations are also given.
E.4.5 The ubiquitous cytokine transforming growth factor-beta1 (TGF1) is associated with P-
glycoprotein expression in certain cancers, increasing the resistance to some chemotherapeutic
agents. TGF1 is one of the most potent metastatic inducers. TGF1 has been shown to increase
A disintegrin and metalloproteinase-12 (ADAM-12) which plays a critical role in cancer growth
and metastasis and is upregulated in many cancers including breast, lung, liver, prostate, gastric,
and bladder. TGF1 activation of NF-κB increases ADAM-12 mRNA expression in breast
111
cancer cells.2731 NF-B is activated by many carcinogens, tumor promoters, and inflammatory
agents associated with cancer development, progression, and drug resistance,2775 as well as by
chemotherapy agents such as paclitaxel.2781 TGF1 has also been associated with decreased
natural killer cell cytotoxicity in gastric cancer patients as cancer progresses.2732 In addition,
chronic injury to normal tissue following treatment by chemotherapy or radiation appears to
involve TGF1 overexpression.2733 [See Appendix E.5.7.] However, since TGF1 acts to
suppress epithelial and possibly other types of tumorigenesis in early stages and multiple
signaling pathways are involved at different stages, TGF1 reduction likely should be restricted
to later stages of tumor progression, invasion, and metastasis,2736 i.e., as part of cancer treatment
but not prevention.
E.4.1 Enhancing therapeutic effects of chemotherapy p. 497
American ginseng root [steamed root ginsenoside Rg3, Rh2] (Panax quinquefolius) – cyclophosphamide
[c]2924,2926
berry [extract with 25% ginsenoside Rb3] − 5-fluorouracil (e)2927
Amla fruit (Emblica officinalis) – cisplatin, doxorubicin (e)2860
Asian ginseng root (red) [c panaxadiol] (Panax ginseng) – 5-fluorouracil [c]3255
Beet root (Beta vulgaris) − doxorubicin (e)3521
Bibhitakhi fruit (Terminalia bellerica) – cisplatin, doxorubicin (e)2860
Chamomile flowers [bisabololoxide A] (Matricaria recutita) –5-fluorouracil [c]2863
Chokeberry fruit (Aronia melanocarpa) − gemcitabine (e)3409
Corn silk/stigma [c maysin] (Zea mays) − camptothecin [c], cisplatin [c], etoposide [c], 5-fluorouracil
[c]3488
Cranberry fruit/juice proanthocyanidins] (Vaccinium macrocarpon) – paraplatin (f)3086
Crucifers like Brussels sprouts, cabbage [c I3C from glucobrassicin, cd DIM (dimer of I3C)] (Brassica
oleracea) – erlotinib, erlotinib [cd]3254
Echinacea purpurea polysaccharides (Echinacea purpurea) – cyclophosphamide2809
Horse chestnut seeds [escin] *(Aesculus hippocastanum) – 5-fluorouracil [c]2776
Milk thistle seeds [silybin(silibinin)] (Silybum marianum) – erlotinib [c] 3354,3355
Sanchi ginseng root [e ethanolic/butanolic extract, c panaxadiol] (Panax notoginseng) − 5-fluorouracil
(e)3256 and [c],3255 irinotecan (e) [not doxorubicin (e)]3256
Shiitake mushrooms [lentinan] (Lentinula edodes) − cisplatin, fluoropyrimidine, paclitaxel3125
Tea green leaves [EGCG &/or ECG] – doxorubicin# [c],3203,3207 erlotinib [c],3356 tamoxifen [c],3467
erlotinib [c],3356-3358 5-fluorouracil [c],2948 paclitaxel [c],3468 raloxifene [c],3470 tamoxifen [c]3468,3469
Tulsi leaves [c vicenin-2] (Ocimum tenuiflorum = Ocimum sanctum) − docetaxel [c]3182
Turmeric rhizome [curcumin] (Curcuma longa, C. aromatica) – capecitabine [c],3115 cisplatin [c],2877
docetaxel [c],3319 gemcitabine [c],3118 oxaliplatin [c],3432 paclitaxel [c],2781 bortezomib,3116
capecitabine,3115 cisplatin [c],2876,2877 docetaxel [c],3319 doxorubicin# (e),2859 etoposide [c] or (e)
and etoposide/temozolomide [c] or (e),3173 gemcitabine (e),3174 [c],3118 oxaliplatin [c],2865
temozolomide [c] or (e) and temozolomide/etoposide [c] or (e)3173
E.4.2 Reducing adverse effects of chemotherapy p. 498
American ginseng root [ginsenoside Rb1, steamed root ginsenoside Rg3, Rh2] (Panax quinquefolius) –
chemotherapy (h), 2916,3293 cyclophosphamide [cs-Rg,Rh],2925,2926 mitomycin C (h),2922
cyclophosphamide [c-Rb]3064
Amla fruit (Emblica officinalis) – cyclophosphamide (e),2853,2955 doxorubicin (e)2859
Ashwagandha root (Withania somnifera) – taxotere/adriamycin/cyclophosphamide (e) and
cyclophosphamide/epirubicin/5-fluorouracil (e)3252
Asian ginseng root (Panax ginseng) – cisplatin (e)2725
Broccoli sprouts [sulforaphane] (Brassica spp.) − cisplatin [c]2934,3403
Calamus rhizome (Acorus calamus) − vincristine (e)3375
112
Cat’s claw bark (Uncaria tomentosa) – doxorubicin (e)3331
Chamomile flowers (Matricaria recutita) – cisplatin (e)3374
Chokeberry fruit [phenolic-rich extract] (Aronia melanocarpa) – cyclophosphamide, doxorubicin3428
Cranberry fruit (Vaccinium macrocarpon) – doxorubicin (e)3080
Echinacea pallida whole plant (Echinacea pallida) – cisplatin (e)2726
French maritime pine bark (Pinus pinaster) – chlorambucil, mitoxantrone and prednisolone3333
Ginger rhizome (Zingiber officinale) – cyclophosphamide,3092,3537 docetaxol,3092,3537 doxorubicin,3537
epirubicin,3092 5-flouracil3537
Ginkgo leaves (Ginkgo biloba) – cisplatin (e)3373
Kudzu root (Pueraria lobata = P. thunbergiana) – cisplatin (e)2724
Lycium (= Goji) fruit [polysaccharides] (Lycium barbarum) − doxorubicin [c],3110 doxorubicin# (j),3029
mitomycin C (f)3030
Mulberry leaf (Morus alba) – doxorubicin (e)2859
Olive leaf (Olea europaea) − intensive chemotherapy (eL)3389
Peppermint leaf oil (Mentha x piperita) – adriamycin, carboplatin, cisplatin, cyclophosphamide,
epirubicin, etoposide, ifosfamide, irinotecan (f)3285
Prickly pear cladode (Opuntia ficus-indica) − (e)3410
Raspberry fruit [ellagic acid] (Rubus idaeus) – cisplatin [c]2864
Reishi mushroom (Ganoderma lucidum) – cisplatin (e)3338
Sage leaves [luteolin] *(Salvia officinalis) – vincristine (e)3372
Soy beans [genistein] (Glycine max) – adriamycin, carboplatin, cisplatin, cyclophosphamide,
dacarbazine, etoposide, ifosfamide, irinotecan, paclitaxel, procarbazine, temozolamide,
vincristine [c]2813
Spearmint leaf oil (Mentha spicata) – adriamycin, carboplatin, cisplatin, cyclophosphamide,
epirubicin, etoposide, ifosfamide, irinotecan (f)3285
Temu lawak rhizome [xanthorrhizol] (Curcuma xanthorrhiza) − cisplatin [c]2950
Tomato fruit [c lycopene] (Lycopersicon esculentum) – cisplatin [c]2864
Tulsi leaves [e methanolic extract] (Ocimum tenuiflorum = Ocimum sanctum) − vincristine (e)3179
Turmeric root [curcumin] (Curcuma longa, C. aromatica) – carboplatin,3485 cisplatin,3363,3407,3485
cyclophosphamide, docetaxel, etoposide,3407 5-fluoruracil,3363,3407 gemicitabine,3363
methotrexate,3407 MOPP/ABVD/COPP, vinblastine & CCNU,3363 taxol,3485 topotecan3407
E.4.3 Selective Cell Retention of Drugs by Inhibiting Efflux Transport Proteins p. 500
Asian ginseng [Note: CORRECTION:, citation #2102 is the following: Choi CH, Kang G, Min Y-D.
Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from
Korean red ginseng. Planta Med., 69:235-240, 2003.]
Hops strobules [prenlflavonoids] (Humulus lupulus) – mitoxantrone (kidney BCRP)3385
Licorice root [c glycyrrhetinic acid] (Glycyrrhiza glabra) − daunorubicin, vinblastine (MDR1),
doxorubicin (MRP1)3368
Milk thistle fruit [pc silymarin] (Silybum marianum) – rosuvastatin (kidney BCRP)2963 [not
rosuvastatin2963]
Mulberry twigs [pc morin] (Morus alba) – paclitaxel (intestine MDR1)2834
Nan wu wei zi fruit [extract and/or c schisandrin B] (Schisandra sphenanthera) ‒ paclitaxel (intestine
MDR1),2827 daunorubicin (leukemia, epidermoid carcinoma, breast cancer MDR1), doxorubicin
(leukemia, epidermoid carcinoma MDR1), epirubicin (leukemia, epidermoid carcinoma MDR1),
homoharringtonine (leukemia, epidermoid carcinoma MDR1), hydroxycamptothecin (leukemia,
epidermoid carcinoma MDR1), mitoxantrone (leukemia, epidermoid carcinoma MDR1), taxol
(leukemia, epidermoid carcinoma, breast cancer MDR1), vincristine (leukemia, epidermoid
carcinoma, breast cancer MDR1)2831
Onion bulbs [c quercetin] (Allium cepa) ‒ paclitaxel (intestine MDR1)2835
113
Schisandra fruit [lignans or c schisandrin B] (Schisandra chinensis) – daunorubicin (leukemia,
epidermoid carcinoma, breast cancer MDR1), doxorubicin (leukemia, epidermoid carcinoma
MDR1), epirubicin (leukemia, epidermoid carcinoma MDR1), homoharringtonine (leukemia,
epidermoid carcinoma MDR1), hydroxycamptothecin (leukemia, epidermoid carcinoma MDR1),
mitoxantrone (leukemia, epidermoid carcinoma MDR1), taxol (leukemia, epidermoid carcinoma,
breast cancer MDR1), vincristine (leukemia, epidermoid carcinoma, breast cancer MDR1)2831
Soy beans [pc genistein] (Glycine max) – paclitaxel (intestine MDR1)2833
Tea green leaves [pc catechins/EGCG, aa theanine] (Camellia sinensis) – doxorubicin and pc (hepatocellular
carcinoma MDR1),3207 tamoxifen and pc (intestine MDR1),3206 doxorubicin [adriamycin] and aa
(ovary GLAST/GLT-1),2949 tamoxifen and pc (breast carcinoma MDR1 & BCRP)3204
Turmeric root [pc curcumin] (Curcuma longa) – etoposide (MRP1 kidney)2945
E.4.4 Promoting and/or Enhancing Chemoprevention of Selective Cancers
p. 501
American ginseng root [4-hour steamed, 70% ethanol extract2923,2996] (Panax quinquefolius) – e/N-acetyl
cysteine, e/vitamin C (colorectal Ca HCT116 and SW480)2923
Apple fruit [fresh (lung and colon)2789] (Malus domestica)
Ashwagandha root [hydroalcoholic extract (skin)3005] (Withania somnifera)
Asian ginseng root [Korean red extract (non-organ-specific in men),2765 red, white powder, fresh, white
extract (lip, oral, pharyngeal, esophageal, stomach, colorectal, liver, pancreatic, laryngeal,
lung, ovaries3325)] (Panax ginseng)
Black raspberry fruit [freeze-dried,2997,3070,3075 ethanol extract,3071,3074,3177 anthocyanins,3071,3072 cs ferulic
acid, beta-sitosterol3177] (Rubus occidentalis)
Broccoli florets/sprouts [sprouts water extract2415,3401,3534 (oral3534) and florets
glucosinolates/isothiocyanates extract (colon),3109 sulphoraphane3402,3534] (Brassica oleracea var.
italica)
Coffee beans roasted [water extract (nonmelanoma skin cancer in white women,2894 ER-neg
postmenopausal breast cancer,2990 liver cancer,2991 glioma [coffee/tea]2992,2993), caffeine
(glioma in men)2992] (Coffea arabica)
Cranberry fruit [juice3100] (Vaccinium macrocarpon)
Crucifers leaves, heads [phenethyl isothiocyanate,2997 indole-3-carbinol (I3C),3399 sulphoraphane3402]
(Brassica spp.)
Cumin seeds [ground3212] (Cuminum cyminum)
Flax seed [whole/ground (breast Ca in women3328)] (Linum usitatissimum)
Kava root (Piper methysticum) [f kavalactones3346]
Milk thistle seeds [silymarin2900,3320] (Silybum marianum)
Prickly pear fruit [water extract3398] (Opuntia spp.)
Reishi [c polysaccharides,1094,2999 triterpenoids2999] (Ganoderma lucidum) – c/liver1094
Shrubby basil leaves [f eugenol-rich oil (topical)3014] (Ocimum gratissimum = O. suave)
Soy beans [isoflavones (prostate cancer)3390] (Glycine max)
Strawberry fruit [freeze-dried (esophageal3339)]
Tea (green or white) leaves [water extracts (colorectal & stomach, esophageal in women,3265 ovarian,
endometrial,3360 ovarian, breast, colorectal, leukemia3380)] (Camellia sinensis)
(black) leaves [water extract ([coffee/tea] glioma),2992,2993 caffeine (glioma in men)2992]
Tulsi leaves [h powder,3212,3216 ae aqueous extract,3216 ee ethanolic extract,3015,3199,3213,3216 em methanolic
extract3180] (Ocimum tenuiflorum = Ocimum sanctum)
Turmeric root [pc curcumin2784,2788,2904] (Curcuma longa)
E.4.5. Reducing Transforming Growth Factor-1 Before,
During, &/or After Chemotherapy p. 502
Astragalus root [water and/or ethanol extracts] (Astragalus membranaceus)– ([e]in rats with Dong quai
[e])2728,2729,2730
114
Dong quai root [water and/or ethanol extracts] (Angelica sinensis) – ([e]in rats with Astragalus
[e])2728,2729,2730
Magnolia bark [honokiol] (Magnolia officinalis) – ([c] in human renal cells)2732
Reishi mushroom [13.5% polysaccharides/6% triterpenes extract] Ganoderma lucidum) – ([e] in human
prostate cancer cells)2737
Turmeric rhizome [curcuminoids (enhanced bioavailability)] (Curcuma longa) − cisplatin,
cyclophosphamide docetaxel, , etoposide, 5-fluoruracil, methotrexate, topotecan3407
115
E.5 Herbals for Preventing and Healing Radiation Adverse Effects
and/or Enhancing Radiotherapy or Photodynamic Therapy
p. 502
Optimal chemoprevention of radiation damage has several features. "A good chemical
protector should be able to protect against the deleterious effect of ionizing radiation during
therapeutic procedures as well as during nuclear accidents, space flight and background
irradiation etc. An ideal radioprotector should be cheap, does not have toxic implications in a
wide dose range, orally administered, rapidly absorbed, possesses a reasonably good dose
reduction factor and can act through multiple mechanisms. The plant and natural products have
all these qualities."3193
Herbal agents can reduce radiation adverse effects in a number of ways. Broad
antioxidant and anti-inflammatory effects are fairly ubiquitous among efficatious plants.
Typically, blood cell parameters are less disrupted by protection of bone marrow progenitor
cells, while preservation and improved regeneration of the gastrointestinal epithelium helps
alleviate the GI syndrome. As a consequence, mortality may be reduced. Recovery rates can be
enhanced as botanical preparations help protect from radiation sickness. One concern about
effective systemic protection is that it theoretically may reduce the therapeutic efficacy of
radiation, but this has yet to be clinically demonstrated with botanical supplements.
E.5.1-5.4 Post-therapeutic or concurrent local applications (L) are applied to treat topical burns
from both heliotherapy and UV lamps and from X-ray and gamma radiation, or to protect or treat
mucositis from gamma radiation.
E.5.3-5.4 Pre-therapeutic use of oral herb preparations (O) or injections (I) has been studied
with exposure to ionizing forms of radiant energy. Some botanicals have been shown to help
protect normal structures and their functions that receive less direct or concentrated irradiation
than the malignant focus.
To differentiate the types of in vivo studies, human cases are in bold and studies in
animals are italicized, while the in vitro tests on cells are in regular type-face. The type of
preparation used is noted. Herbal preparations may be the powdered herb (h), fresh gel or juice
(j), a solvent extract (e), an extract fraction (f) or an isolated component (c). Clinical trials with
negative results [neg.] are shown in brackets.
E.5.5-5.6 In some instances, the botanical can serve as a synergistic antitumor agent, or it may
improve the post-treatment radiation sensitivity and therapeutic response in certain malignant
tissues.
E.5.7 Chronic injury to normal tissue following treatment by chemotherapy or radiation appears
to involve transforming growth factor-beta 1 (TGF1) overexpression.2733 [See Appendix E.4.5
introduction.] Increases in TGF1 during radiation treatment for non-small cell lung cancer is
indicative of significant reduction in survival time,2734 and significant TGF1 elevations after
radiation therapy have been correlated with symptomatic radiation pneumonitis.2735
E.5.9-5.10 ^ Topical and internal herbal preparations that help prevent UV overexposure and
the consequent inflammation and aging and increased risk of skin cancer by blocking the
radiation or quenching free radicals are covered here in the context of passive exposure to solar
radiation. These should not be use when actively exposing skin lesions to UV phototherapy, due
to the counterproductive aspect of simultaneously reducing the therapeutic effect. However,
internal use of herbal antioxidants shown to protect against UV damage may be useful in some
cases.
116
Damage to the skin from solar radiation is well known following acute or chronic
exposure. Ultraviolet (UV)-induced skin damage is associated with inflammation and the
generation of reactive oxygen species or free radicals. An imbalance between reactive oxygen
species generation and cellular antioxidant capacity leads to oxidative stress that contributes to
carcinogenesis. Excessive skin exposure to UV can cause DNA damage, cell-cycle arrest,
apoptosis, depletion of antioxidant defenses, immunosuppression, and proinflammatory cytokine
release. Acute sunburn is attributed to the UVB spectrum (280-320 nm) that only penetrates the
epidermis and makes up about 5% of solar UV. However, UVB is 1000 times more carcinogenic
to the skin than UVA due to free radical damage. Both melanoma and nonmelanoma skin
cancers can arise from UVB damage. The aging from chronic solar radiation is largely attributed
to the UVA spectrum (320-400 nm), comprising 90-95% of solar UV. Chronic overexposure to
UVA radiation leads to increases in skin pigmentation, thickness, wrinkling, and melanoma risk
due to its deep penetration into the dermis of the skin.2867,3001
Currently, commercial sunscreens applied topically reduce skin cancer risk by partially
blocking UV radiation but are inadequate alone for preventing dermal carcinogenesis. Some
sunscreens do not block UVA, so, though helping prevent sunburn, squamous cell carcinoma,
and basal cell carcinoma, increased time in the sun and exposure to UVA can lead to higher risk
of melanoma, the most virulent form of skin cancer. Since UV creates oxidative stress in the
skin, the use of dietary and herbal antioxidants orally (O) and/or topically (T) may help
reduce the risk of skin cancer as well as inflammation and erythema (sunburn) from solar
radiation. In vitro studies of UV radiation done on human keratinocyte cultures are designated as
topical treatments.
(Based on major references: 2867, 3001, 3193)
E.5.4. Protection from Adverse Effects of Gamma Radiation p. 504
Aloe leaf gel (Aloe vera) – [neg. Lj 2772,2773,2774
]
American ginseng root (Panax quinquefolius) – Te3065,3066
Amla fruit [aqueous extract,2850,2852 methanol extract2851] (Emblica officinalis) – Oe2850,2851,2852
Asian ginseng root (Panax ginseng) – Ie, If,3323 Ic3324
Bael leaf, fruit (Aegle marmelos) – Oe, Ie3193
Cat’s claw bark (Uncaria tomentosa) – Oe3330
Corn silk/stigma [ethanolic extract] (Zea mays) − Oe3487
Cranberry fruit extract (Vaccinium macrocarpon) – Oe3266
Dong quai roots (Angelica sinensis) – Of3365
Frankincense resin extract (Boswellia serrata) – Oe,2846 Le3498
Ginkgo leaves (Ginkgo biloba) – Oe, Ie3193
Gulancha herb (Tinospora cordifolia) – Oe3193
Jambolan seeds, leaf (Syzygium cumini) – Oe, Ie3193
Long pepper fruit (Piper longum) – Ie3194
Milk thistle seeds [flavolignan fraction] (Silybum marianum) – If, Of2903
Neem berry [oil] (Azadirachta indica) − Le3430
Peppermint leaf [oil] (Mentha x piperita) – Of3195
Rajgira leaf (Amaranthus paniculatus) – Oe3193
Sea buckthorn fruit [hydroethanolic extract] (Hippophae rhamnoides) – Ie3000
Soy bean [f isoflavones, c genistein] (Glycine max) ‒ Of,2812 Of /c2813
St. John's wort flower [extract] (Hypericum perforatum) − Le3430
Sweet basil leaves (Ocimum basilicum) − Oe3180
Tomato fruit [c lycopene] (Lycopersicon esculentum) – Oc2769
Tulsi leaves [ea aqueous extract, em methanolic-aqueous extract, c vicenin, orientin] (Ocimum
tenuiflorum = Ocimum sanctum) – Oc,3408 Oem,3180 Iea,3214 Ic3215
117
[Note CORRECTION: The current scientific name for Tulsi, also identified as Holy basil on p.
377, is Ocimum tenuiflorum but was formerly Ocimum sanctum.]
Turkey tail mycelia (Trametes versicolor) – Oh3211
Turmeric root (Curcuma longa) – Lc,3485 Oc,3359,3363 Oc,3121 Oe3318
E.5.5 Enhancing Antineoplastic Effects of Radiation p. 504
Black raspberry fruit [methanol extract] (Rubus occidentalis) – Lc [breast adenocarc.]3081
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) – Oe [melanoma]3180
Turmeric root (Curcuma longa) – Lc [ovarian],2876 Lc [colorectal],2866,2875 Oc [Note CORRECTION:
colorectal]2676
E.5.7. Reducing Transforming Growth Factor-1 Before,
During, &/or After Radiotherapy p. 505
Astragalus root [water and/or ethanol extracts] (Astragalus membranaceus)– ([e]in rats with Dong quai
[e])2728,2729,2730
Dong quai root [water and/or ethanol extracts] (Angelica sinensis)– ([e]in rats with Astragalus
[e])2728,2729,2730
Magnolia bark [honokiol] (Magnolia officinalis) – ([c] in human renal cells)2732
Reishi mushroom [13.5% polysaccharides/6% triterpenes extract] Ganoderma lucidum) – ([e] in human
prostate cancer cells)2737
E.5.9 Potential Herbal Prevention of Dermal Photocarcinogenesis NEW ^
Black raspberry fruit [80% ethanol extract3071] (Rubus occidentalis) − Te [after UVB irradiation]3073
Bloodroot root [c sanguinarine] (Sanguinaria canadensis) − Tc3008
Broccoli sprouts [e; c sulforaphane] (Brassica oleracea v. italica) ‒ Tc, Te,c3037
Coffee beans (roasted) [e aqueous] (Coffea arabica) ‒ Oe2894
Ginger rhizome [c 6-gingerol] (Zingiber officinale) − Tc, Tc3010
Grapes fruit [c resveratrol] (Vitis spp.) ‒ Tc,2886,2887,2888,2897 Tc2889
Grape seed [e ethanolic extract; f proanthocyanidin] ‒ Of,2885 Te3016
Heather herb [e ethanolic extract] (Calluna vulgaris) − Te3016
Olive leaf [e; c oleuropein], fruit [f oil] (Oleo europaea) ‒ Oe,c2868 Tf [after irradiation]2870
Pomegranate juice/seed [extract, c delphinidin] (Punica granatum) – Tc, Tc,3007 Te3006
Milk thistle seed [f silymarin; c silybin] (Silybum marianum) ‒ Tf,2871,2872,2873 Tc2891,3009,3010,3011
Soy beans [c genistein] (Glycine max) – Tc3017,3018
Tea (green) leaves [e aqueous; f polyphenols; c EGCG] (Camellia sinensis) ‒ Tf,2890 Tf,2873,2880
Tc,2884,3003,3016 Oe,2874,2883,3004 Of2880,2881
Tea (black) leaves [e aqueous] ‒ Oe,2892,2893 Oe2882,2883
Turmeric root [pc curcumin] (Curcuma longa) ‒ Tc2878
E.5.10 Herbal Prevention of Acute UV-induced Erythema NEW ^
Broccoli sprouts [e; c sulforaphane] (Brassica oleracea v. italica) ‒ Te, Te,c 2895
Cocoa bean (fermented, roasted) [h/f flavanols] (Theobroma cacao) ‒ Oh/f2911

Grapes fruit [c resveratrol] (Vitis spp.) ‒ Tc2886
Lycium (= Goji) berries (Lycium barbarum) − Oj3028
Rhatany root (Krameria triandra) − Te3176
Tea (green) leaves [f polyphenols or catechins] (Camellia sinensis) ‒ Tfp,2890 Ofc3361
E.5.11 Herbal Protection Against Radioiodine Therapy Adverse Effects NEW ^
Ginkgo leaf extract (Ginkgo biloba) – Oe3095,3096
Tulsi leaves (Ocimum tenuiflorum = Ocimum sanctum) – Oe3184, 3186
118
E.6 Herbals and Anti-infection Agents p. 505
Methicillin-resistant Staphylococcus aureus (MRSA) infections have recently spread
from their common occurrence in hospitals to growing prevalence in the community, including
schools. There are now also vancomycin resistant Staph. aureus (VRSA) strains. Other
bacterial strains have become multiple drug-resistant (MDR), such as MDR Staph. aureus
varieties resistant to mupirocin and/or other antibiotics as well as to methicillin (MDR-MRSA).
Vancomycin-resistant Enterococci (VRE) are another example of bacterial transformations
causing concerns about treating infections for which a commonly used antibiotic is ineffective.
With increasing failures of antibiotic treatment for some bacterial infections, new or
alternative agents and practices are being investigated to help address this growing vulnerability.
In particular, combinations of antibiotics are necessary to control some infections and prevent
epidemics of diseases like tuberculosis. The disadvantage of using single molecule antimicrobial
drugs for infectious disease control is now recognized, based on a microbes ability to rapidly
develop resistance to the a single compound and its mechanism of activity. While complex plant
extracts typically lack the comparative potency of single-molecule antimicrobial drugs, the
pluripotent complexity and multiple pharmacodynamic impact on the infectious process offers
the advantage, inherently developed in the plants themselves, of resisting infections over the long
term. In addition, when combined with conventional antimicrobial medication, they may
complement the drug pharmacology or enhance its effects by improving its absorption, half-life,
and/or microbial cellular retention. Conversely, it is possible that for certain drugs and/or
particular microbes an extract that is beneficial in some circumstances can be a disadvantage in
others by antagonizing ordinary pharmacotherapy. Ongoing research is needed to unveil the
potential of beneficial combinations and potential disruptions when combining plant preparations
with antimicrobial therapeutic agents.3031
The normal typeset for the botanical and other antimicrobial agent(s) indicates in
vitro studies, while italicizing is used for in vivo animal studies, and bold type indicates
human clinical studies. In the case of combinations with antimicrobial agents, abbreviations
are used for the botanical forms, whether it be the herb (h), an extract (e), a fraction (f), or
a component (c) or several components (cs), and for the name of the associated
antimicrobial.
^E.6.11 Antimicrobial agents including antibiotics are capable of inducing a variety of adverse
effects, depending on the agent. This can limit their life-saving potential by restricting the
effective dose required for optimal treatment. Botanicals that are capable of reducing
antimicrobial toxicity can help in the acute and/or chronic treatment of infections. The specific
herbal preparation, toxic antimicrobial, and protected organ(s) from in vitro (plain type),
animal (italicized) or human (bold) studies are listed after each botanical. Probiotic
microorganisms are not considered in this category, though they can be of great benefit in
reducing adverse enteric effects and recovering from disrupted intestinal flora from antibiotic
use.
(Additional major references: 3031)
E.6.1 Botanicals active against antibiotic-resistant strains of bacteria

p. 507
Ajowan fruit (Carum copticum) e methanol extract − (e) MDR-Salmonella typhi3046
Alstonia stem bark (Alstonia scholaris) f hexane fraction of methanolic extract − (f) MDR-
Enterobacteriacea bacterium IK1_01, (f) MDR-Shigella dysenteriae, (f) MDR-Enterobacter
cloacae, (f) MDR-Serratia marcescens3235
119
Andrographis leaf (Andrographis paniculata) e aqueous extract − (e) MRSA2974
Arjun tree leaves (Terminalia arjuna) e methanol extract − (e) MDR-Salmonella typhi3046
Bael fruit pulp (Aegle marmelos) e methanol or aqueous extracts − (e) MDR-Salmonella typhi3046
Bibhitaki fruit (Terminalia belerica) ee ethanolic extract – (ee) MDR-MRSA3200
Black cherry bark (Prunus serotina) ee ethanolic extract – (ee) MDR-Neisseria gonorrhoeae3326
Black nightshade seeds *(Solanum nigrum) e methanol extract − (e) MDR-Salmonella typhi3046
Cassia bark (Cinnamomum cassia) c cinnamaldehyde − (c) MDR-Salmonella typhimurium, (c) MDR-E.
coli, (c) MDR-Staph. aureus, (c) erythromycin-resistant Strep. pyogenes3047
Catechu bark (Acacia catechu) e methanol extract − (e) MDR-Salmonella typhi3046
Celandine herb (Chelidonium majus) cs 8-hydroxydihydrosanguinarine, 8-hydroxydihydrochelerythrine –
(cs) MRSA3370
Celery leaves (Apium graveolens) e methanol extract − (e) MDR-Salmonella typhi3046
Chamomile herb (Matricaria recutita) e extract − (e) methicillin-resistant Staph. epidermidis3327
Chaparral leaves [c NDGA/lignins] (Larrea tridentata) − (c) MRSA, (c) MDR-Mycobacterium
tuberculosis3102
Chicory leaves (Cichorium intybus) e methanol extract − (e) MDR-Salmonella typhi3046
Chinese lantern tree fruit (Dichrostachys glomerata) e methanolic extract − (e) MDR-Escherichia coli,
(e) MDR-Enterbacter aerogenes, (e) MDR-Klebsiella pneumoniae, (e) MDR-Pseudomonas
aeruginosa3020
Chinese rhubarb root (Rheum palmatum) cs emodin & rhein – (cs) MRSA3336
Chinese skullcap root (Scutellaria baicalensis) c baicalin – (e) MDR-Acinetobacter baumannii,2719 (c)
MRSA, (c) penicillin-resistant Staphylococcus aureus2358
Cinnamon bark (Cinnamomum verum) c cinnamaldehyde − (c) MDR-Salmonella typhimurium, (c) MDR-
E. coli, (c) MDR-Staph. aureus, (c) erythromycin-resistant Strep. pyogenes3047
Cinnamon beilschmiedia bark (Beilschmiedia cinnamomea) e methanolic extract − (e) MDR-E. coli, (e)
MDR-Enterbacter aerogenes, (e) MDR-K. pneumoniae3020
Clary sage root (Salvia sclarea) (e) extract, cs salvipisone, aethiopinone − (c) MRSA, (c) MDR-Staph.
epidermidis,3036 (e) methicillin-resistant Staph. epidermidis3327
Clove bud (Syzygium aromaticum) c eugenol − (c) MDR-Salmonella typhimurium, (c) MDR-E. coli, (c)
MDR-Staph. aureus, (c) erythromycin-resistant Strep. pyogenes3047
Coriander fruit (Coriandrum sativum) f essential oil – (f) MRSA3262
Eucalyptus leaf (Eucalyptus globulus) f essential oil – (f) MRSA,2712 (f) Mycobacterium tuberculosis2714
fruit essential oil, 1,8-cineole &/or aromadendrene – (f, cs, c-a) MRSA, VRE (Enterococcus
faecalis)2713
Garlic bulb *(Allium sativum) e water extract – (e) MDR-Mycobacterium tuberculosis,3170 (c) isoniazid-
resistant Mycobacterium tuberculosis3172
Goldenseal root and rhizome *(Hydrastis canadensis) ee ethanolic extract, c berberine – (ee, c) MDR-
Neisseria gonorrhoeae3326
leaves: e hydroethanolic extract, c berberine − (e,c) MRSA3130
Gotu kola leaves (Centella asiatica) e methanol extract − (e) MRSA2974
Haritaki fruit (Terminalia chebula) ee ethanolic extract – (ee) MDR-MRSA3200
Horseradish root (Armoracia rusticana) c allyl isothiocyanate − (c) MDR-Salmonella typhimurium, (c)
MDR-E. coli, (c) MDR-Staph. aureus, (c) erythromycin-resistant Strep. pyogenes3047
Indian nettle leaves (Acalypha indica) e aqueous extract − (e) MDR-Mycobacterium tuberculosis3170
Kikar bark (Acacia nilotica) e aqueous extract − (e) MDR-Salmonella typhi3046
Kutaki leaves (Picrorrhiza kurroa) e methanol or aqueous extracts − (e) MDR-Salmonella typhi3046
Licorice root (Glycyrrhiza uralensis) c gancaonin – (c-ga) vancomycin-resistant strains of Enterococcus
faecalis, E. faecium, E. gallinarum and MRSA3032
Magnolia bark (Magnolia officinalis) e extract – (e) MDR-Acinetobacter baumannii2719
Malabar nut leaves (Adhatoda vasica) e aqueous extract − (e) MDR-Mycobacterium tuberculosis3170
120
Mongolian mulberry (Morus mongolica) cs mulberrofurans − (c) vancomycin-resistant strains of
Enterococcus faecalis, E. faecium, E. gallinarum and MRSA3032
Mustard seed (Brassica nigra) c allyl isothiocyanate − (c) MDR-Salmonella typhimurium, (c) MDR-E.
coli, (c) MDR-Staph. aureus, (c) erythromycin-resistant Strep. pyogenes3047
Orange rind (Citrus sinensis) f essential oil − f MRSA, VRSA3146
Oregano herb (Origanum vulgare ssp. hirsutum) c caravcrol or thymol – (c-c&t) MDR-Salmonella
typhimurium, (c-c&t) MDR-E. coli, (c-c&t) MDR-Staph. aureus, (c-c&t) erythromycin-resistant
Strep. pyogenes3047
Pomegranate fruit peel (Punica granatum) ee ethanolic extract, em methanol extract – (ee) MDR-
MRSA,3200 (em) MDR-Salmonella typhi3046
Rabdosia (Rabdosia rubescens) – (e) MDR-Acinetobacter baumannii2719
Rhodiola root (Rhodiola rosea) ee ethanolic extract – (ee) MDR-Neisseria gonorrhoeae3326
Rugose rose flower (Rosa rugosa) – (e) MDR-Acinetobacter baumannii2719
Sage leaf (Salvia officinalis) e extracts − (e) methicillin-resistant Staph. epidermidis3327
Simal bark (Salmalia malabarica) e methanol extract − (e) MDR-Salmonella typhi3046
Southern prickly ash (Zanthoxylum clava-herculis) e alkaloidal extract, f ethyl acetate, c chelerythrine −
(ea, fe, c) MDR-MRSA3421
Sowa seed (Peucedanum graveolens) e methanol extract − (e) MDR-Salmonella typhi3046
Star anise fruit (Illicium verum) e supercritical CO2 extract, f diethylether fraction, c anethole − (e) MDR-
Acinetobacter baumannii, (f) MDR-Acinetobacter baumannii, (f) MDR-Pseudomonas
aeruginosa, (f) MRSA, (c) MDR-Acinetobacter baumannii3249
Sweet tea fruit (Rubus chingii) – (e) MDR-Acinetobacter baumannii2719
Tea leaf (b black, o Oolong and/or g green) leaf (Camellia sinensis) ea aqueous extract, ee ethanolic
extract, fa acetone fraction, fm methanol fraction – (ee, fa, fm) MDR-MRSA,3200 (ea) MDR-
Acinetobacter baumannii2719
Thyme herb (Thymus vulgaris) f essential oil, c thymol or caravcrol – (f) MRSA,2712 (c-t&c) MDR-
Salmonella typhimurium, (c-t&c) MDR-E. coli, (c-t&c) MDR-Staph. aureus, (c-t&c)
erythromycin-resistant Strep. pyogenes3047
Tropical almond fruit (Terminalia chebula) – (e) MDR-Acinetobacter baumannii2719
Tulsi seed (Ocimum tenuiflorum = Ocimum sanctum) ea aqueous extract, ee ethanolic extract, ec
chloroform extract, c eugenol − (ee) MDR-MRSA,3200 (ea) MDR-Salmonella typhi,3046 (ee, ec)
MDR-Neisseria gonorrhoeae,3307 (c) MDR-Neisseria gonorrhoeae3306
Turmeric rhizome (Curcuma longa) e ethyl acetate extract − (e) MRSA3250
Usnea lichen (Usnea spp.) c usnic acid – MRSA3376
Uva ursi leaf (Arctostaphylos uva-ursi) ee ethanolic extract – (ee) MDR-Neisseria gonorrhoeae3326
Viranga fruit (Embelia ribes) e methanol and aqueous extracts − (e) MDR-Salmonella typhi3046
E.6.2 Botanicals improving antimicrobial efficacy against resistant strains
p. 508
Bibhitaki fruit (Terminalia belerica) ee ethanolic extract – ee/tetracycline & MDR-MRSA3200
Cassia bark (Cinnamomum cassia) c cinnamaldehyde − c/tetracycline & MDR-E. coli, c/ampicillin or
penicillin & MDR-Staph. aureus3047
Chamomile herb (Matricaria recutita) e extract − e/oxacillin & methicillin-resistant Staph.
epidermidis3327
Chinese lantern tree fruit (Dichrostachys glomerata) e methanolic extract − (e) MDR-Escherichia coli,
(e) MDR-Enterbacter aerogenes, (e) MDR-Klebsiella pneumoniae, (e) MDR-Pseudomonas
aeruginosa3020
Chinese rhubarb root (Rheum palmatum) cs emodin & rhein – cs/ampicillin or oxacillin & MRSA3336
Cinnamon bark (Cinnamomum verum) c cinnamaldehyde − c/tetracycline & MDR-E. coli, c/ampicillin or
penicillin & MDR-Staph. aureus3047
Cinnamon beilschmiedia bark (Beilschmiedia cinnamomea) e methanolic extract − (e) MDR-E. coli, (e)
MDR-Ent. aerogenes, (e) MDR-K. pneumoniae3020
121
Clary sage roots (Salvia sclarea) e extract, c salvipisone or aethiopinone − e/oxacillin & methicillin-
resistant Staph. epidermidis,3327 c-s or c-a/oxacillin, vancomycin, or linezolid & MRSA, MDR-
Staph. epidermidis3036
Clove bud (Syzygium aromaticum) c eugenol − c/penicillin & MDR-Staph. aureus 3047
Goldenseal leaves *(Hydrastis canadensis) e hydroethanolic extract − e/berberine & MRSA3130
Haritaki fruit (Terminalia chebula) ee ethanolic extract – ee/tetracycline & MDR-MRSA3200
Horseradish root (Armoracia rusticana) c allyl isothiocyanate − c/ampicillin or erythromycin & MDR-
Salmonella typhimurium, c/bacitracin & MDR-E. coli, c/bacitracin & MDR-Staph. aureus3047
Khat leaves (Catha edulis) e aqueous extract − e/tetracycline & Strep. oralis and Strep. sanguis,
e/penicillin-G & Fusobacterium nucleatum3033
Kutaki roots/rhizome (Picrorhiza kurroa) f iridoid glycosides − f/chloroquine & MDR-Plasmodium
yoelii2937
Lesser galangal rhizome (Alpinia officinarum) c galangin − c/gentamicin & MRSA3039
Mustard seed (Brassica nigra) c allyl isothiocyanate − c/ampicillin or erythromycin & MDR-Salmonella
typhimurium, c/bacitracin & MDR-E. coli, c/bacitracin & MDR-Staph. aureus3047
Oregano herb (Origanum vulgare ssp. hirsutum) c caravcrol or thymol – c-c/novobiocin, penicillin, or
tetracycline & MDR-Salmonella typhimurium, c-c/penicillin or tetracycline and c-t/erythromycin
& MDR-E. coli, c-c&t/ampicillin, bacitracin, or penicillin & MDR-Staph. aureus, c-
c&t/erythrocycin & erythromycin-resistant Strep. pyogenes3047
Pomegranate fruit peel (Punica granatum) ee ethanolic extract – ee/tetracycline & MDR-MRSA3200
Sage leaf (Salvia officinalis) e extracts, eo essential oil − e,eo/oxacillin & methicillin-resistant Staph.
epidermidis3327
Sappan wood (Caesalpinia sappan) e methanol extract – e/ampicillin or oxacillin & MRSA2720
Shirazian thyme herb (Zataria multiflora) – f/vancomycin & MRSA2715
Tea (green) leaf (Camellia sinensis) ee ethanolic extract, c EGCG – ee/tetracycline & MDR-MRSA,3200 c-
E/imipenem & imipenem-resistant Klebsiella pneumoniae2968
Thyme herb (Thymus vulgaris) c thymol or caravcrol – c-c/novobiocin, penicillin, or tetracycline &
MDR-Salmonella typhimurium, c-c/penicillin or tetracycline and c-t/erythromycin & MDR-E.
coli, c-t&c/ampicillin, bacitracin, or penicillin & MDR-Staph. aureus, c-t&c/erythrocycin &
erythromycin-resistant Strep. pyogenes3047
Turmeric rhizome (Curcuma longa) e ethyl acetate extract − e/-lactams (oxacillin or ampicillin) &
MRSA3250
E.6.3 Botanicals enhancing the ordinary efficacy of antibiotics & antiseptics
p. 510
Ashwagandha root (Withania somnifera) – h/ethambutol, isoniazid, pyrazinamide, and rifampicin &
Mycobacterium tuberculosis3233
Barberry root bark (Berberis vulgaris) c berberine – c/sulphacetamide & Chlamydia trachoma577
Bilberry leaves (Vaccinium myrtillus) e aqueous acetone, c gallic acid − e,c/linezolid, vancomycin &
Staph. aureus3422
Cinnamon (Cinnamomum spp.) f essential oil − f/chlorhexidine & Streptococcus mutans, Lactobacillus
plantarum3035
Clary sage roots (Salvia sclarea) c salvipisone or aethiopinone − c/oxacillin & Staph. aureus, Staph.
epidermidis3036
Clove oil (Syzygium aromaticum) c eugenol − c/ampicillin, chloramphenicol, erythromycin, norfloxacin,
oxacillin, penicillin, polymyxin B, rifampin, tetracycline, vancomycin & Enterobacter aerogenes,
Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhimurium2956
[methanolic extract antagonized the activity of cefoxitin, ciprofloxacin, and gentamicin against E.
coli3349]
Cola seed (Cola nitida) e methanolic extract – e/ciprofloxacin, perfloxacin, levofloxacin & E. coli3034
Coptis root (Coptis spp.) c berberine – c/sulphacetamide & Chlamydia trachoma577
122
Coriander fruit (Coriandrum sativum) f essential oil – f/chloramphenicol, ciprofloxacin, gentamicin or
tetracycline & Acinetobacter baumannii3263
Garlic clove *(Allium sativum) h fresh cut, e water extract – local h/chorhexidine & group B
Streptococcus,2711 e/isoniazid/rifampicin/ethambutol/pyrazinamide & Mycobacterium
tuberculosis,3169 e/isoniazid or rifampicin & Mycobacterium tuberculosis,3171 me/gentamicin & E.
coli3349
Geranium leaf (Pelargonium graveolens) f essential oil − f/norfloxacin & Bacillus subtilis, Bac. cereus,
Staph. aureus or E. coli3041
Goldenseal root and rhizome *(Hydrastis canadensis) c berberine – c/sulphacetamide & Chlamydia
trachoma577
Maitake mushroom (Grifola frondosa) f D-fraction – f/vancomycin & Listeria monocytogenes3340
Manuka (Leptospermum scoparium) f essential oil − f/chlorhexidine & Streptococcus mutans,
Lactobacillus plantarum3035
Oregon grape bark (Mahonia [or Berberis] spp.) c berberine – c/sulphacetamide & Chlamydia
trachoma577
Peppermint (Mentha piperita) f essential oil, c menthol − f/ciprofloxacin = 1-1.5 & Klebsiella
pneumoniae, f/ciprofloxacin ≥ 1 & Staph. aureus,2689 f/oxytetracylcine & E. coli,
c/oxytetracycline and E. coli3042
[f/ciprofloxacin < 0.5 or ≥ 4 reduced antibiotic activity against Klebsiella pneumoniae;
f/amphotericin B reduced antifungal effect Candida albicans2689]
Rosemary leaf (Rosmarinus officinalis) f essential oil – f/ciprofloxacin < 3 & Klebsiella pneumoniae2689
[f/ciprofloxacin reduced antibiotic activity against Staph. aureus; f/amphotericin B reduced
antifungal effect on Candida albicans2689]
Star anise fruit (Illicium verum) f diethylether fraction − f/amikacin & Pseudomonas aeruginosa,
f/amoxillin, ampicillin, clindamycin, or pipericillin & Staph. aureus3249
Tea (green) leaf (Camellia sinensis) c catechin EGCG – c/ciprofloxacin & E. coli3038
Tea tree (Melaleuca alternifolia) f essential oil − f/tobramycin & Staph. aureus, f/tobramycin & E.
coli,3040 f/ciprofloxacin = 1.5 & Klebsiella pneumoniae2689
[f/ciprofloxacin < 1 reduced antibiotic activity against Klebsiella pneumoniae; f/ciprofloxacin
reduced antibiotic activity against Staph. aureus; f/amphotericin B reduced antifungal effect on
Candida albicans2689]
Thyme (Thymus vulgaris) f essential oil − f/ciprofloxacin = 1-1.5 & Klebsiella pneumoniae2689
[f/ciprofloxacin ≤ 1.5 reduced antibiotic activity against Staph. aureus; f/amphotericin B reduced
E.6.6 Botanicals inhibiting efflux of antimicrobial agents by bacteria
Goldenseal leaves (Hydrastis canadensis) cs sideroxylin, 6- and 8-desmethyl-sideroxylin − e/berberine &
NorA Staph. aureus,3236 e/berberine & NorA MRSA,3296 cs/berberine NorA MRSA3297
E.6.7 Botanicals enhancing [or reducing] the efficacy of antifungal agents p. 512
Agastache herb (Agastache rugosa) f essential oil, c estragole – f,c/ketoconazole & Blastoschizomyces
capitatus3051
Barberry bark (Berberis spp.) c berberine – c/fluconazole & Candida albicans,3106 c/amphotericin B &
Candida albicans3107
Coptis rhizome (Coptis chinensis) c berberine – c/fluconazole & Candida albicans,3106 c/amphotericin B
& Candida albicans3107
Goldenseal roots/rhizome *(Hydrastis canadensis) c berberine – c/fluconazole & Candida albicans,3106
c/amphotericin B & Candida albicans3107
Mediterranean spurge stem (Euphorbia characias) f latex − f/ketoconazole & Candida albicans3055
Moroccan thyme herbs (Thymus maroccanus, T. broussonetii) f essential oils – f/fluconazol or
amphotericin B & Candida albicans2716
Myrtle leaves (Myrtus communis) f essential oil – f/amphotericin B & Candida albicans or Aspergillus
niger2718
123
Oregano herb (Origanum vulgare) f essential oil – f/amphotericin B & Candida spp.,3052 f/nystatin &
Candida spp.3053
Oregon grape root bark (Mahonia spp.) c berberine – c/fluconazole & Candida albicans,3106
c/amphotericin B & Candida albicans3107
Peppermint (Mentha piperita) f essential oil, c menthol − [f/amphotericin B reduced antifungal effect
Candida albicans2689]
Pomegranate fruit peel (Punica granatum) e hydroalcoholic extract, f ethyl acetate, c punicalagin –
e,f,c/fluconazole & Candida albicans, c/ketoconazole & Candida albicans3049
[not c/nystatin or amphotericin B & Candida albicans3049]
Rose geranium leaf (Pelargonium graveolens) f essential oil, c geraniol or citronellol − c-g,c-
c/ketoconazole & Aspergillus flavus,3050 f/amphotericin B & Candida spp.,3052 f/nystatin &
Candida spp.3053
Rosemary leaf (Rosmarinus officinalis) f essential oil – [f/amphotericin B reduced antifungal activity
against Candida albicans2689]
Santolina aerial parts (Santolina chamaecyparissus) f essential oil − f/clotrimazole & Candida
albicans3054
Tea (green) leaf (Camellia sinensis) [Note: CORRECTION – catechin EGCG in Tea, not in Tea tree leaf]
catechin EGCG – c/amphotericin B or fluconazole & Candida albicans2366
Tea tree leaf (Melaleuca alternifolia) f essential oil [Note: CORRECTION – catechin EGCG not in Tea
tree leaf. See Tea above.] – f/amphotericin B & Candida spp.3052
[f/amphotericin B reduced antifungal effect on Candida albicans2689]
Thyme leaf (Thymus vulgaris) f essential oil – [f(uncharacterized chemotype)/amphotericin B reduced
Tulsi leaves (Ocimum tenuiflorum = O. sanctum) f essential oil (methyl chavicol chemotype), c methyl
chavicol or linalool – f,c/fluconazol or ketoconazole & Candida spp. or MDR-Candida spp.2717
E.6.8 Botanicals enhancing efficacy of antiviral agents p. 512
Clove oil (Syzygium aromaticum) c eugenol − c/acyclovir & herpes simplex virus types 1 & 2 2955
E.6.9 Botanicals enhancing the efficacy of immunizations against infections p. 512

Larch bark (Larix spp.) cs arabinogalactans – pneumococcal vaccine2739
E.6.10.a Botanicals reducing adhesion of bacteria that cause infections p. 512
Black horehound herb (Ballota nigra) e aqueous extract − MRSA3350
Cranberry fruit (Vaccinium macrocarpon) j juice, jc juice cocktail, f high molecular weight compounds –
jc (E.coli),3002 j (Streptococcus criceti, Strep. gordonii, Strep. mitis, Strep. mutans, Strep oralis,
Strep. sanguinis, Strep. sobrinus);2843 f-hmw (Porphyromonas gingivalis),2841 (Strep.
sobrinus)2842
Motherwort leaves (Leonurus cardiaca) e aqueous-acetone (30:70) extract, c ursolic acid − e
(Staphylococcus aureus), c (Staph. aureus)3460
Tassel hyacinth bulb (Leopoldia comosa) ae aqueous extract, ee ethanolic extract − ae MRSA, ee
MRSA3350
E.6.10.b Botanicals inducing exocytosis of intracellular bacteria that prolong infections
NEW ^
Coleus [formerly Makandi] leaf (Coleus forskohlii) c forskolin − c (Eschericia coli)3295
E.6.11 Botanicals reducing adverse effects caused by antimicrobial agents NEW
^
Ashwagandha root (Withania somnifera) – e/gentamicin3253
Black cumin seed oil (Nigella sativa) c thymoquinone – c/gentamicin3259
Cordyceps (Cordyceps sinensis) h mycelium, e water extract – h/amikacin (kidney), h/gentamicin
(kidney), h/gentamicin (kidney), e/kanamycin (kidney)598
124
Garlic leaves or cloves *(Allium sativum) h-c cloves, h-l leaves, e aged extract, c diallyl sulfide or diallyl
disulfide – h/gentamicin,1911,3387 c-ds or c-dd/gentamicin,1912,1913 e/gentamicin1914,1915
Gentian root (Gentiana lutea) hydroethanolic extract − e/ketoconazole3353
Ginkgo leaf (Ginkgo biloba) e standardized extract − e/gentamicin, e/gentamicin3260
Milk thistle seed (Silybum marianum) f silymarin ‒ f/metronidazole (stomach, liver, kidney)2267
Spiny sowthistle herb (Sonchus asper) e methanolic extract − e/gentamicin (kidney, liver)3019
125
References
2709. Zhou P, Gross S, Liu J-H, et al. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-
sensitive oxidative stress through modulation of IKK/NF-B and MAPK signaling pathways. FASEB J.,
24:4722-2732, 2010
2710. Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother. Res., 24:475-480, 2010
2711. Cohain JS. Case series: symptomatic group B streptococcus vaginitis treated with fresh garlic. Integrat. Med.,
9(3):40-43, 2010
2712. Tohidpour A, Sattari M, Omidbaigi R, et al . Antibacterial effect of essential oils from two medicinal plants
against methicillin-resistant Staphylococcus aureus (MRSA). Phytomed., 17:142-145, 2010
2713. Mulyaningsih S, Sporer F, Zimmermann S, et al. Synergistic properties of the terpenoids aromadendrene and
1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-
resistant pathogens. Phytomed., 17:1061-1066, 2010
2714. Sherry E, Warnke PH. Successful use of an inhalational phytochemical to treat pulmonary tuberculosis: a case
report. Phytomed., 11:95-97, 2004
2715. Mahboubi M, Bidgoli FG. Antistaphylococcal activity of Zataria multiflora essential oil and its synergy with
vancomycin. Phytomed., 17:548-550, 2010
2716. Saad A, Fadli M, Bouaziz M, et al. Anticandidal activity of the essential oils of Thymus maroccanus and
Thymus broussonetii and their synergism with amphotericin B and fluconazol. Phytomed., 17:1057-1060,
2010
2717. Amber K, Aijaz A, Immaculata X, et al. Anticandidal effect of Ocimum sanctum essential oil and its synergy
with fluconazole and ketoconazole. Phytomed., 17:921-925, 2010
2718. Mahboubi M, Bidgoli FG. In vitro synergistic efficacy of combination of amphotericin B with Myrtus
communis essential oil against isolates of Candida albicans. Phytomed., 17:771-774, 2010
2719. Miyasaki Y, Nichols WS, Morgan MA, et al. Screening of herbal extracts against multi-drug resistant
Acinetobacter baumannii. Phytother. Res., 24:1202-1206, 2010
2720. Kim K-J, Yu H-H, Jeong S-I, et al. Inhibitory effects of Caesalpinia sappan on growth and invasion of
methicillin-resistant Staphylococcus aureus. J. Ethnopharmacol., 91:81-87, 2004
2721. Belcaro G, Cesarone MR, Dugall M, et al. Product-evaluation registry of Meriva®, a curcumin-
phosphatidylchole complex, for the complementary management of osteoarthritis. Panminerva Med., 52(2
Suppl 1):55-62, 2010
2722. Jacquet A, Girodet P-O, Pariente A, et al. Phytalgic®, a food supplement, vs placebo in patients with
osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial. Arthr. Res
Ther., 11:R192, 2009
2723. Leelarungrayub D, Pratanaphon S, Pothongsunun P, et al. Vernonia cinerea Less. supplementation and
strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in
active smokers. J. Int. Soc. Sports Nutr., 7:21, 2010
2724. Yu H-H, Jung S-Y, Shin M-K, et al. Pueraria thunbergiana inhibits cisplatin-induced damage of HEI-OC1
auditory cells through scavenging free radicals. Phytother. Res., 24:834-839, 2010
2725. Im GJ, Chang JW, Choi J, et al. Protective effect of Korean red ginseng extract on cisplatin ototoxicity in
HEI-OC1 auditory cells. Phytother. Res., 24:614-621, 2010
2726. Mustea I, Postescu ID, Tamas M, et al. Experimental evaluation of protective activity of Echinacea pallida
against cisplatin toxicity. Phytother. Res., 11:263-265, 1997
2727. Wu Y-L, Jiang Y-Z, Jin X-J, et al. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects
acetaminophen-induced hepatic toxicity in mice. Phytomed., 17:475-479, 2010
2728. Wojcikowski K, Wohlmuth H, Johnson DW, et al. Effect of Astragalus membranaceus and Angelica sinensis
combined with enalapril in rats with obstructive uropathy. Phytother. Res., 24:875-884, 2010
2729. Wang H, Li J, Yu L, et al. Antifibrotic effect of the Chinese herbs, Astragalus mongholicus and Angelica
sinensis, in a rat model of chronic puromycin aminonucleoside nephrosis. Life Sci., 74:1645-1658, 2004
2730. Zhang YW, Xie D, Xia B, et al. Suppression of transforming growth factor-1 gene expression by danggui
buxue tang, a traditional Chinese herbal preparation, in retarding the progress of renal damage in
streptozotocin-induced diabetic rats. Horm. Metab. Res., 38:82-88, 2006
2731. Ray A, Khar S, Ray BK. Transforming growth factor-1-mediated activation of NF-B contributes to
enhanced ADAM-12 expression in mammary carcinoma cells. Mol. Cancer Res., 8(9):1261-1270, 2010
2732. Szkaradkiewicz A, Karpinski TM, Drews M, et al. Natural killer cell cytotoxicity and immunosuppressive
cytokines (IL-10, TGF1) in patients with gastric cancer. J. Biomed. Biotechnol., #901564:1-7, 2010
126
2733. Anscher MS. Targeting the TGF-1 pathway to prevent normal tissue injury after cancer therapy. Oncologist,
15:350-359, 2010
2734. Zhao L, Ji W, Zhang L, et al. Changes of circulating transforming growth factor-beta 1 level during radiation
therapy are correlated with the prognosis of locally advance non-small cell lung cancer. J. Thorac. Oncol.,
5(4):521-525, 2010
2735. Kim J-Y, Kim Y-S, Kim Y-K, et al The TGF-1 dynamics during radiation therapy and its correlation to
symptomatic radiation pneumonitis in lung cancer patients. Radiat. Oncol.,4:59, 2009
2736. Joshi A, Cao D. TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect.
Front. Biosci., 15:180-194, 2010
2737. Stanley G, Harvery K, Slivova V, et al. Ganoderma lucidum suppresses angiogenesis through the inhibition of
secretion of VEGF and TGF-1 from prostate cancer cells. Biochem. Biophys. Res. Commun., 330:46-52,
2005
2738. Ma SW, Benzie IF, Chu TT, et al. Effect of Panax ginseng supplementation on biomarkers of glucose
tolerance, antioxidant status and oxidative stress in type 2 diabetic subjects: results of a placebo-controlled
human intervention trial. Diab. Obes. Metab., 10:1125-1127, 2008
2739. Udani JK, Singh BB, Barrett JL, et al. Proprietary arabinogalactan extract increases antibody response to the
pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.
Nutrit. J., 9:32, 2010
2740. Mellor DD, Sathyapalan T, Kilpatrick ES, et al. High-cocoa polyphenol-rich chocolate improves HDL
cholesterol in type 2 diabetes patients. Diabet. Med., 27:1318-1321, 2010
2741. Kim K, Kim H, Kwon J, et al. Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse
model of non-insulin-dependent diabetes mellitus. Phytomed., 16:856-863, 2009
2742. Kapetanovic IM, Crowell JA, Krishnaraj R, et al. Exposure and toxicity of green tea polyphenols in fasted
and non-fasted dogs. Toxicol., 260:28-36, 2009
2743. Isbrucker RA, Edwards JA, Wolz E, et al. Safety studies on epigallocatechin gallate (EGCG) preparations.
Part 2: Dermal, acute and short-term studies. Food Chem Toxicol., 44:636-650, 2006
2744. Wu K-M, Yao J, Boring D. Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs. Int. J.
Toxicol., 30(1):19-20, 2011
2745. Lynch ME. Cannabis reduces opioid dose in the treatment of chronic non-cancer pain. J. Pain Symptom
Manage., 25(6):496-498, 2003
2746. Reisfield GM, Wasan AD, Jamison RN. The prevalence and significance of cannabis use in patients
prescribed chronic opioid therapy: A review of the extant literature. Pain Med., 10(8):1434-1441, 2009
2747. Sproule BA, Usoa E, Somer G, et al. Characteristics of dependent and nondependent regular users of codeine.
J. Clin. Psychopharm., 19(4):367-372, 1999
2748. Nurmikko TJ, Serpell MG, Hoggart B, et al. Sativex successfully treats neuropathic pain characterised by
allodynia: A randomised, double-blind, placebo-controlled trial. Pain, 133:210-220, 2007
2749. Holdcroft A, Maze M, Dore C, et al. A multicenter dose-escalation study of the analgesic and adverse effects
of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiol., 104:1040-1046,
2006
2750. Lynch ME, Clark AJ. A case series of patients using medicinal marihuana for management of chronic pain
under the Canadian Marihuana Medical Access Regulations. J. Pain Sympt. Manag., 32(5):497-501, 2006
2751. Kavia RBC, DeRidder D, Constantinescu CS, et al. Randomized controlled trial of Sativex to treat detrusor
overactivity in multiple sclerosis. Multiple Scler., online prepub., Sep. 9, 2010
2752. Adhikary B, Yadav SK, Roy K, et al. Black tea and theaflavins assist healing of indomethacin-induced gastric
ulceration in mice by antioxidative action. eCAM, online; doi:10.1155/2011/546560, 2011
2753. Lee B, Yang CH, Hahm D-H, et al. Inhibitory effects of Coptidis rhizoma and berberine on cocaine-induced
sensitization. eCAM 691):85-90, 2009
2754. Hauer J, Anderer FA. Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from
Larix occidentalis. Cancer Immunol. Immunother., 36:237-244, 1993
2755. Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. Altern.
Med. Rev., 4(2):96-103, 1999
2756. Asdaq SM, Inamdar MN. Potential of garlic and its active constituent, S-allyl cysteine, as antihypertensive
and cardioprotective in presence of captopril. Phytomed., 17:1016-1026, 2010
2757. Ried K, Frank OR, Stocks NP. Aged garlic extract lowers blood pressure in patients with treated but
uncontrolled hypertension: A randomised controlled trial. Maturitas, 67(2):144-150, 2010
127
2758. Akilen R, Tsiami A, Devendra D, et al. Glycated haemoglobin and blood pressure-lowering effect of
cinnamon in multi-ethnic type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-
blind clinical trial. Diab. Med., 27:1159-1167, 2010
2759. Maskatia ZK, Baker K. Hypereosinophilia associated with echinacea use. South. Med. J., 103(11):1173-1174,
2010
2760. Singh V, Singh SP, Chan K. Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic
schizophrenia. Int. J. Neuropsychopharm., 13:257-271, 2010
2761. Zuo X-C, Zhang B-K, Jia S-J, et al. Effects of Ginkgo biloba extracts on diazepam metabolism: a
pharmacokinetic study in healthy Chinese male subjects. Eur. J. Clin. Pharmacol., 66:503-509, 2010
2762. Lei H-P, Ji W, Lin J, et al. Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy
volunteers. Br. J. Clin. Pharmacol., 68(2):201-206, 2009
2763. Ansell J, McDonough M, Zhao Y, et al. The absence of an interaction between warfarin and cranberry juice: a
randomized, double-blind trial. J. Clin. Pharmacol., 49:824-830, 2009
2764. Bilgi N, Bell K, Ananthakrishnan AN, et al. Imatinib and Panax ginseng: a potential interaction resulting in
liver toxicity. Ann. Pharmacother., 44:926-928, 2010
2765. Yun T-K, Zheng S, Choi S-Y, et al. Non-organ-specific preventive effect of long-term administration of
Korean red ginseng extract on incidence of human cancers. J. Med. Food., 13(3):489-494, 2010
2766. Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a
retrospective review of the California Poison Control System reported cases. Ann. Pharmacother., 44:1022-
1029, 2010
2767. Wan R-z, Zhou M-j, Liu C-x. The effects of salvianolic acid B from Radix Salvia Miltiorrhizae on the oral
pharmacokinetics of metoprolol and metoprolol acid in rats. Phytother. Res., 24:846-851, 2010
2768. Sun D-X, Fang Z-Z, Zhang Y-Y, et al. Inhibitory effects of curcumenol on human liver cytochrome P450
enzymes. Phytother. Res., 24:1213-1216, 2010
2769. Saada HN, Rezk RG, Eltahawy NA. Lycopene protects the structure of the small intestine against gamma-
radiation-induced oxidative stress. Phytother. Res., 24:S204-S208, 2010
2770. Wang X, Cheung CM, Lee WYW, et al. Major tanshinones of danshen (Salvia miltiorrhiza) exhibit different
modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomed.,
17:868-875, 2010
2771. Wan C-K, Tse AK, Yu Z-L, et al. Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin
A isolated from Fructus Schisandrae chinensis. Phytomed., 17:702-705, 2010
2772. Williams MS, Burk M, Loprinzi CL, et al. Phase III double-blind evaluation of an Aloe vera gel as a
prophylactic agent for radiation-induced skin toxicity. Int. J. Radiat. Oncol. Biol. Phys., 36(2):345-349,
1996
2773. Bosley C, Smith J, Baratti P, et al. A phase III trial comparing an anionic phospholipid-based (APP) cream
and Aloe vera-based gel in the prevention and treatment of radiation dermatitis. Int. J. Radiat. Oncol. Biol.
Phys., 57(2; Suppl.):S438, 2003
2774. Heggie S, Bryant GP, Tripcony L, et al. A phase III study on the efficacy of topical Aloe vera gel on irradiated
breast tissue. Cancer Nurs., 25(6):442-451, 2002
2775. Luqman S, Pezzuto JM. F: a promising target for natural products in cancer chemoprevention. Phytother.
Res., 24:949-963, 2010
2776. Ming ZJ, Hu Y, Qiu YH, et al. Synergistic effects of -aescin and 5-fluorouracil in human hepatocellular
carcinoma SMMC-7721 cells. Phytomed., 17:575-580, 2010
2777. Ampasavate C, Sotanaphun U, Phattanawasin P, et al. Effects of Curcuma spp. on P-glycoprotein function.
Phytomed., 17:506-512, 2010
2778. Zhang W, Tan TMC, Lim L-Y. Impact of curcumin-induced changes in P-glycoprotein and CYP3A
expression on the pharmacokineteics of peroral celiprolol and midazolam in rats. Drug Metab. Dispos.,
35(1):110-115, 2007
2779. Zhang W, Lim L-Y. Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-
mediated metabolism in vitro. Drug Metab. Dispos., 36(7):1283-1290, 2008
2780. Hou Z-L, Takahashi K, Tanaka K, et al. Curcuma drugs and curcumin regulate the expression and function of
P-gp in Caco-2 cells in completely opposite ways. Int. J. Pharmaceut., 358:224-229, 2008
2781. Aggarwal BB, Shishodia S, Takada Y, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-B
pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin.
Cancer Res., 11(20):7490-7498, 2005
128
2782. Li L, Ahmed B, Mehta K, et al. Liposomal curcumin with and without oxaliplatin: effects on cell growth,
apoptosis, and angiogenesis in colorectal cancer. Mol. Cancer Ther., 6(4):1276-1282, 2007
2783. Sharma RA, Ireson CR, Verschoyle RD, et al. Effects of dietary curcumin on glutathione S-transferase and
malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels. Clin. Cancer
Res., 7:1452-1458, 2001
2784. Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett., 255:170-181, 2007
2785. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic
activity and compliance. Clin. Cancer Res., 10:6847-6854, 2004
2786. Garcea G, Berry DP, Jones DJL, et al. Consumption of th e putative chemopreventive agent curcumin by
cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic
consequences. Cancer Epidem. Biomark. Prev., 14(1)120-125, 2005
2787. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, et al. Efficacy and safety of Curcuma
domestica extracts in patients with knee osteoarthritis. J. Altern. Compl. Med., 15(8):891-897, 2009
2788. Malhotra A, Nair P, Dhawan DK. Modulatory effects of curcumin and resveratrol on lung carcinogenesis in
mice. Phytother. Res., 24:1271-1277, 2010
2789. Gerhauser C. Cancer cehemopreventive potential of apples, apple, juice, and apple components. Planta Med.,
74:1608-1623, 2008
2790. Kumar PP, Kuttan G. Vernonia cinerea L. scavenges free radicals and regulates nitric oxide and
proinflammatory cytokines profile in carrageenan induced paw edema model. Immunopharmacol.
Immunotoxicol., 31(1):94-102, 2009
2791. Doyle BJ, Frasor J, Bellows LE, et al. Estrogenic effects of herbal medicines from Costa Rica used for the
management of menopausal symptoms. Menopause, 16(4):748-755, 2009
2792. Zhou S-F, Xue CC, Yu X-Q, et al. Metabolic activation of herbal and dietary constituents and its clinical and
toxicological implications: an update. Curr. Drug Metab., 8:526-553, 2007
2793. Molto J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and
darunavir/ritonavir in HIV-infected patients. Antimicrob. Agents Chemother., 55(1):326-330, 2011
2794. Belcaro G, Cesarone MR, Ricci A, et al. Control of edema in hypertensive subjects treated with calcium
antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol. Clin. appl.
Thromb./Hemost., 12(4):440-444, 2006
2795. Farid R, Mirfeizi Z, Mirheidari M, et al. Pycnogenol supplementation reduces pain and stiffness and
improves physical function in adults with knee osteoarthritis. Nutrit. Res., 27:692-697, 2007
2796. Isbaniah F, Wiyono WH, Yunus F, et al. Echinacea purpurea along with zinc, selenium and vitamin C to
alleviate exacerbations of chronic obstructive pulmonary disease: results from a randomized controlled
trial. J. Clin. Pharm. Ther., [epub. ahead of print; doi:10.1111/j.1365-2710.2010.01212.x] 2010
2797. Sood A, Ebbert JO, Prasad K, et al. A randomized clinical trial of St. John's wort for smoking cessation. J.
Altern. Compl. Med., 16(7):1-7, 2010
2798. Bajorek SA, Morello CM. Effects of dietary fiber and low glycemic index diet on glucose control in subjects
with type 2 diabetes mellitus. Ann. Pharmacother., 44:1786-1791, 2010
2799. Ziai SA, Larijani B, Akhoondzadeh S, et al. Psyllium decreased serum glucose and glycosylated hemoglobin
significantly in diabetic outpatients. J. Ethnopharmacol., 102:202-207, 2005
2800. Anderson JW, Allgood LD, Turner J, et al. Effects of psyllium on glucose and serum lipid responses in men
with type 2 diabetes and hypercholesterolemia. Am. J. Clin. Nutr., 70:4666-473, 1999
2801. Pastors JG, Blaisdell PW, Balm TK, et al. Psyllium fiber reduces rise in postprandial glucose and insulin
concentrations in patients with non-insulin-dependent diabetes. Am. J. Clin. Nutr., 53:1431-1435, 1991
2802. Belcaro G, Cesarone MR, Dugall M, et al. Efficacy and safety of Meriva ®, a curcumin-phosphatidylcholine
complex, during extended administration in osteoarthritis patients. Altern. Med. Rev., 15(4):337-344, 2010
2803. Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral
phospholipidic curcumin treatment. Long-term follow-up. Clin. Ophthamol., 41-6, 2010
2804. Sengupta K, Krishnaraju AV, Vishal AA, et al. Comparative efficacy and tolerability of 5-Lozin® and
Aflapin® against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study.
Int. J. Med. Sci., 7(6):366-377, 2010
2805. Widrig R, Suter A, Saller R, et al. Choosing between NSAID and arnica for topical treatment of hand
osteoarthritis in a randomised, double-blind study. Rheumatol. Int., 27:585-591, 2007
2806. Juan H, Terhaag B, Cong Z, et al. Unexpected effect of concomitantly administered curcumin on the
pharmacokinetics of talinolol in healthy Chinese volunteers. Eur. J. Clin. Pharmacol., 63:663-668, 2007
129
2807. Tuntipopipat S, Judprasong K, Zeder C, et al. Chili, but not turmeric, inhibits iron absorption in young women
from an iron-fortified composite meal. J. Nutrit., 136:2970-2974, 2006
2808. Chaiyata P, Puttadechakum S, Komindr S. Effect of chili pepper (Capsicum frutescens) ingestion on plasma
glucose response and metabolic rate in Thai women. J. Med. Assoc. Thai., 85(9):854-860, 2003
2809. Razina TG, Lopatina KA, Zueva AM, et al. Effect of Echinacea purpurea tincture and its polysaccharide
complex on the efficacy of cutyostatic therapy of transferred tumors [abstract only; article in Russian].
Eksp. Klin. Farmakol., 70(3):33-35m 2007
2810. Chow H-HS, Hakim IA, Vining DR, et al. Effects of repeated green tea catechin administration on human
cytochrome P450 activity. Cancer Epidemiol. Biomarkers Prev., 15(12):2473-2476, 2006
2811. Huyen VT, Phan DV, Thang P, et al. Antidiabetic effect of Gynostemma pentaphyllum tea in randomly
assigned type 2 diabetic patients. Horm. Metab. Res., 42(5):353-357, 2010
2812. Ahmad IU, Forman JD, Sarkar FH, et al. Soy isoflavones in conjunction with radiation therapy in patients
with prostate cancer. Nutr. Cancer., 62(7):996-1000, 2010
2813. Tacyildiz N, Ozyoruk D, Yavuz G, et al. Soy isoflavones ameliorate the adverse effects of chemotherapy in
children. Nutr. Cancer, 62(7):1001-1005, 2010
2814. Rostock M, Fischer J, Mumm A, et al. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast
cancer patients with climacteric complaints - a prospective observational study. Gyn. Endocrin.,
27(10):844-848, 2011
2815. Lu FR, Shen L, Qin Y, et al. Clinical observation of Trigonella foenum-graecum L. total saponins in
combination with sulfonylureas in the treatment of type 2 diabetees mellitus [abstract]. Chin. J. Integr.
Med., 14(1):56-60, 2008
2816. Stiborova M, Frei E, Wiessler M, et al. Human enzymes involved in the metabolic activation of carcinogenic
aristolochic acids: evidence for reductive activation by cytochromes P450 1A1 and 1A2. Chem. Res.
Toxicol., 14:1128-113, 2001
2817. Hashimoto K, Higuchi M, Makino B, et al. Quantitative analysis of aristolochic acids, toxic compounds,
contained in some medicinal plants. J. Ethnopharm., 64:185-189, 1999
2818. Nortier JL, Martinez M-CM, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese
herb (Aristolochia fangchi). N. Engl. J. Med., 342(23):1686-1691, 2000
2819. Ioannides C, Delaforge M, Parke DV. Safrole: its metabolism, carcinogenicity and interactions with
cytochrome P-450. Fd. Cosmet. Toxicol., 19:657-666, 1981
2820. To LP, Hunt TP, Andersen ME. Mutagenicity of trans-anethole, estragole, eugenol, and safrole in the Ames
Salmonella typhimurium assay. Bull. Environm. Contam. Toxicol., 28:647-654, 1982
2821. Khojasteh-Bakht SC, Chen W, Koenigs LL, et al. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran
by human liver cytochrome P-450s: evidence for formation of a furan epoxide. Drug Metab. Dispos.,
27(5):574-580, 1999
2822. Fau D, Lekehal M, Farrell G, et al. Diterpenoids from germander, an herbal medicine, induce apoptosis in
isolated rat hepatocytes. Gastroent., 113:1334-1346, 1997
2823. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton
pump inhibitor drugs (PPIs). http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm; Mar. 2, 2011
2824. Avizeh R, Najafzadeh H, Razijalali M, et al. Evaluation of prophylactic and therapeutic effects of silymarin
and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats. J. Vet. Pharmacol. Therap., 33:95-
99, 2009
2825. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results
of a controlled, double-blind, randomized and multicenter trial. J. Hepatol., 28:615-621, 1998
2826. Butterweck V, Semlin L, Feistel B, et al. Comparative evaluation of two different Opuntia ficus-indica
extracts for blood sugar lowering effects in rats. Phytother. Res., 25:370-375, 2011
2827. Jin J, Bi H, Hu J, et al. Effect of wuzhi tablet (Schisandra sphenanthera extract) on the pharmacokinetics of
paclitaxel in rats. Phytother. Res., [online prepub. doi:10.1002/ptr.3407] 2011
2828. Qin X-l, Bi H-c, Wang C-x, et al. Study of the effect of wuzhi tablet (Schisandra sphenanthera extract) on
tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method. Biomed.
Chromat., 24:399-405, 2010
2829. Xin H-W, Wu X-C, Li Q, et al. Effects of Schisandra sphenanthera extract on the pharmacokinetics of
tacrolimus in healthy volunteers. Br. J. Clin. Pharmacol., 64(4):469-475, 2007
2830. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of wuzhi tablet
(Schisandra sphenanthera extract) on the absortpion and first-pass intestinal and hepatic metabolism of
tacrolimus (FK506). Int. J. Pharmaceut., 389:114-121, 2010
130
2831. Qiangrong P, Wang T, Lu Q, et al. Schisandrin B ‒ a novel inhibitor of P-glycoprotein. Biochem. Biophys.
Res. Comm., 335:406-411, 2005
2832. Lai L, Hao H, Wang Q, et al. Effects of short-term and long-term pretreatment of Schisandra lignans on
regulating hepatic and intestinal CYP3A in rats. Drug Metab. Dispos., 37(12):2399-2407, 2009
2833. Li X, Choi J-S. Effect of genistein on the pharmacokinetics of paclitaxel administered orally or intravenously
to rats. Int. J. Pharmaceut., 337:188-193, 2007
2834. Choi B-C, Choi J-S, Han H-K. Altered pharmacokintetics of paclitaxel by the concomitant use of morin in
rats. Int. J. Pharmaceut., 323:81-85, 2006
2835. Choi J-S, Jo B-W, Kim Y-C. Enhanced paclitaxel bioavailability after oral administration of paclitaxel or
prodrug to rats pretreated with quercetin. Eur. J. Pharmaceut. Biopharm., 57:313-318, 2004
2836. Lu Z, Jia Q, Wang R, et al. Hypoglycemic activities of A- and B-type procyanidin oligomer-rich extracts from
different cinnamon barks. Phytomed., 18:298-302, 2011
2837. Xin W, Zhang L, Sun F, et al. Escin exerts synergistic anti-inflammatory effects with low doses of
glucocorticoids in vivo and in vitro. Phytomed., 18:272-277, 2011
2838. Melese E, Asres K, Asad M, et al. Evaluation of the antipeptic ulcer activity of the leaf extract of Plantago
lanceolata L. in rodents. Phytother. Res., online prepub. doi:10.1002/ptr.3411, 2011
2839. Lee IS, Park S, Park K, et al. Hepatoprotective activity of Scutellariae radix extract in mice fed a high fat diet
with chronic alcohol exposure. Phytother. Res., online prepub. doi:10.1002/ptr.3370, 2011
2840. Xie L, Chen M-H, Li J, et al. Antithrombotic effect of a polysaccharide fraction from Laminaria japonica
from the South China Sea. Phytother. Res., online prepub. doi:101002/ptr.3433, 2011
2841. Labrecque J, Bodet C, Chandad F, et al. Effects of a high-molecular-weight cranberry fraction on growth,
biofilm formation and adherence of Porphyromonas gingivalis. J. Antimicrob. Chemother., 58:439-443,
2006
2842. Steinberg D, Feldman M, Ofek I, et al. Cranberry high molecular weight constituents promote Streptococcus
sobrinus desorption from artificial biofilm. Int. J. Antimicrob. Agents, 25:247-251, 2005
2843. Yamanaka A, Kimizuka R, Kato T, et al. Inhibitory effects of cranberry juice on attachment of oral
streptococci and biofilm formation. Oral Microbiol. Immunol., 19:150-154, 2004
2844. Tang J, Dunlop RA, Rowe A, et al. Kavalactones yangonin and methysticin induce apoptosis in human
hepatocytes (HepG2) in vitro. Phytother. Res., 25:417-423, 2011
2845. Hyun TK, Eom SH, Yu CY, et al. Hovenia dulcis - an Asian traditional herb. Planta Med., 76:943-949, 2010
2846. Kirste S, Treier M, Wehrle SJ, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain
tumors. Cancer, online prepub. doi:10.1002/cncr.25945, 2011
2847. Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy. Neurol.,
68:515-521, 2007
2848. Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized,
crossover clinical trial. Neuropsychopharm., 34:672-680, 2009
2849. Heeba GH, Abd-Elghany MI. Effect of combined administration of ginger (Zingiber officinale Roscoe) and
atorvastatin on the liver of rats. Phytomed., 17:1076-1081, 2010
2850. Singh I, Sharma A, Nunia V, et al. Radioprotection of Swiss albino mice by Emblica officinalis. Phytother.
Res., 19:444-446, 2005
2851. Hari Kumar KB, Sabu MC, Lima PS, et al. Modulation of haematopoetic system and antioxidant enzymes by
Emblica officinalis Gaertn and its protective role against -radiation induced damages in mice. J. Radiat.
Res., 45:549-555, 2004
2852. Jindal A, Soyal D, Sharma A, et al. Protective effect of an extract of Emblica officinalis against radiation-
induced damage in mice. Int. Cancer Ther., 8(1);98-105, 2009
2853. Sharma N, Trikha P, Athar M, et al. Inhibitory effect of Emblica officinalis on the in vivo clastogenicity of
benzo[a]pyrene and cyclophosphamide in mice. Hum. Exp. Toxicol., 19:377-384, 2000
2854. Banu SM, Selvendiran K, Singh JPV, et al. Protective effect of Emblica officinalis ethanolic extract against
7,12-dimethylbenz[a]anthracene (DMBA) induced genotoxicity in Swiss albino mice. Hum. Exp. Toxicol.,
23:527-531, 2004
2855. Haque R, Bin-Hafeez B, Ahmad I, et al. Protective effects on Emblica officinalis Gaertn. in
cyclophosphamide-treated mice. Hum Exp. Toxicol., 20:643-650, 2001
2856. Pramyothin P, Samosorn P, Poungshompoo S, et al. The protective effects of Phyllanthus emblica Linn.
extract on ethanol induced rat hepatic injury. J. Ethnopharmacol., 107:361-364, 2006
131
2857. Panchabhai TS, Ambarkhane SV, Joshi AS, et al. Protective effect of Tinospora cordifolia, Phyllanthus
emblica and their combination against antitubercular drugs induced hepatic damage: an experimental study.
Phytother. Res., 22:646-650, 2008
2858. Tasduq SA, Kaisar P, Gupta DK, et al. Protective effect of a 50% hydroalcoholic fruit extract of Emblica
officinalis against anti-tuberculosis drugs induced liver toxicity. Phytother. Res., 19:193-197, 2005
2859. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, et al. Screening of antioxidants from medicinal plants
for cardioprotective eefect against doxorubicin toxicity. Bas. Clin. Pharmicol. Toxicol., 96:80-87, 2005
2860. Pinmai K, Chunlaratthanabhorn S, Ngamkitidechakul C, et al. Synergistic growth inhibitory effect of
Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents: doxorubicin and
cisplatin against human hepatocellular carcinoma and lung cancer cells. World J. Gastroenterol., 14:1491-
1497, 2008
2861. Qiu D, Zhao G, Aoki Y, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression
at the level of purine-box/nuclear factor of activated T-cells and NF-B transcriptional activation. J. Biol.
Chem., 274(19):13443-13450, 1999
2862. Titov DV, Gilman B, He Q-L, et al. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat.
Chem. Biol., 7:182-188, 2011
2863. Ogata-Ikeda I, Seo H, Kawanai T, et al. Cytotoxic action of bisabololoxide A of German chamomile on
human leukemia K562 cells in combination with 5-fluorouracil. Phytomed., 18:362-365, 2011
2864. Turk G, Ceribasi AO, Sahna E, et al. Lycopene and ellagic acid prevent testicular apoptosis induced by
cisplatin. Phytomed., 18:356-361, 2011
2865. Li L, Ahmed B, Mehta K, et al. Liposomal curcumin with and without oxaliplatin: effects on cell growth,
apoptosis, and angiogenesis in colorectal cancer. Mol. Cancer Ther., 6(4):1276-1282, 2007
2866. Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitized human colorectal cancer xenografts
in nude mice to -radiation by targeting nuclear factor-B-regulated gene products. Clin. Cancer Res.,
14(7):2128-2136, 2008
2867. Baliga MS, Katiyar SK. Chemoprevention of photocarcinogenesis by selected botanicals. Photochem.
Photobiol., 5:243-253, 2006
2868. Sumiyoshi M, Kimura Y. Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet
B irradiation-induced skin changes in C57BL/6J mice. Phytother. Res., 24:995-1003, 2010
2869. Dinkova-Kostova AT. Phytochemicals as protectors against ultraviolet radiation: versatility of effects and
mechanisms. Planta Med., 74:1548-1559, 2008
2870. Budiyanto A, Ahmed NU, Wu A, et al. Protective effect of topically applied olive oil against
photocarcinogenesis following UVB exposure of mice. Carcinogen., 21(11):2085-2090, 2000
2871. Katiyar SK, Korman NJ, Mukhtar H, et al. Protective effects of silymarin against photocarcinogenesis in a
mouse skin model. J. Nat. Cancer Inst., 89(8):556-565, 1997
2872. Katiyar SK. Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression
and oxidative stress in mouse skin. Int. J. Oncol., 21:1213-1222, 2002
2873. Chatterjee ML, Agarwal R, Mukhtar H. Ultraviolet B radiation-induced DNA lesions in mouse epidermis: an
assessment using a novel 32P-postlabelling technique. Biochem. Biophys. Res. Comm., 229:590-595, 1996
2874. Conney AH, Wang Z-Y, Huang M-T, et al. Inhibitory effect of green tea on tumorigenesis by chemicals and
ultraviolet light. Prev. Med., 21:361-369, 1992
2875. Sandur SI, Deorukhkar A, Pandey MK, et al. Curcumin modulates the radiosensitivity of colorectal cancer
cells by suppressing constitutive and inducible NF-B activity. Int. J. Radiation Oncol. Biol Phys.,
75(2):534-542, 2009
2876. Yallapu MM, Maher DM, Sundram V, et al. Curcumin induces chemo/radio-sensitization in ovarian cancer
cells and curcumin nanoparticles inhibit ovarian cancer cell growth. J. Ovarian Res., 3(11), 2010
2877. Duarte VM, Han E, Veena MS, et al. Curcumin enhances the effect of cisplatin in suppression of head and
neck squamous cell carcinoma via inhibition of IKK protein of the NFB pathway. Mol. Cancer Ther.,
9(10):2665-2675, 2010
2878. Oda Y. Inhibitory effect of curcumin on SOS functions induced by UV irradiation. Mutat. Res., 348:67-73,
1995
2879. Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata
(Passionflower) herbal tea on subjective sleep quality. Phytother. Res., online prepub.
doi:10.1002/ptr.3400, 2011
2880. Wang ZY, Agarwal R, Bickers DR, et al. Protection against ultraviolet B radiation-induced
photocarcinogenesis in hairless mice by green tea polyphenols. Carcinogen., 12(8):1527-1530, 1991
132
2881. Agarwal R, Katiyar SK, Khan SG, et al. Protection against ultraviolet B radiation-induced effects in the skin
of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea. Photochem Photobiol.,
58(5):695-700, 1993
2882. Record IR, Dreosti IE. Protection by tea against UV-A + B-induced skin cancers in hairless mice. Nutrit.
Cancer, 32(2):71-75, 1998
2883. Wang ZY, Huang M-T, Lou Y-R, et al. Inhibitory effects of black tea, green tea, decaffeinated black tea, and
decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-
dimethylbenz[a]anthracene-initiated SKH-1 mice. Cancer Res., 54:3428-3435, 1994
2884. Mittal A, Piyathilake C, Hara Y, et al. Exceptionally high protection of photocarcinogenesis by topical
application of (‒)-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model:
relationship to inhibition of UVB-induced global DNA hypomethylation. Neoplasia, 5(6):555-565, 2003
2885. Mittal A, Elmets CA, Katiyar SK. Dietary feeding of proanthocyanidins from grape seeds prevents
photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation.
Carcinogen., 24(8):1379-1388, 2003
2886. Afaq F, Adhami VM, Ahmad N. Prevention of short-term ultraviolet B radiation-mediated damages by
resveratrol in SKH-1 hairless mice. Toxicol. Appl. Pharmacol., 186:28-37, 2003
2887. Reagan-Shaw S, Afaq F, Aziz MH, et al. Modulations of critical cell cycle regulatory events during
chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mice skin.
Oncogene, 23:5151-5160, 2004
2888. Aziz MH, Afaq F, Ahmad N. Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is
mediated via modulation in survivin. Photochem. Photobiol., 81:25-31, 2005
2889. Adhami VM, Afaq F, Ahmad N. Suppression of ultraviolet B exposure-mediated activation of NF-B in
normal human keratinocytes by resveratrol. Neoplasia, 5(1):74-82, 2003
2890. Katiyar SK, Perez A, Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of
ultraviolet light B-induced pyrimidine dimers in DNA. Clin. Cancer Res., 6:3864-3869, 2000
2891. Mallikarjuna G, Dhanalakshmi S, Singh RP, et al. Silibinin protects against photocarcinogenesis via
modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Cancer Res.,
64:6349-6356. 2004
2892. Hakim IA, Harris RB, Weisgerber UM. Tea intake and squamous cell carcinoma of the skin: influence of type
of tea beverages. Cancer Epidemiol. Biomarkers Prev., 9:727-731, 2000
2893. Rees JR, Stukel TA, Perry AE, et al. Tea consumption and basal cell and squamous cell skin cancer: Results
of a case-control study. J. Am Acad. Dermatol., 56:781-785, 2007
2894. Abel EL, Hendrix SO, McNeeley SG, et al. Daily coffee consumption and prevalence of nonmelanoma skin
cancer in Caucasian women. Eur. J. Cancer Prev., 16:446-452, 2007
2895. Talalay P, Fahey JW, Healy ZR, et al. Sulforaphane mobilizes cellular defenses that protect skin against
damage by UV radiation. Proc. Nat. Acad. Sci., 104(44):17500-17505, 2007
2896. Kinkova-Kostova AT, Fahey JW, Wade KL, et al. Induction of the phase 2 response in mouse and human skin
by sulforaphane-containing broccoli sprout extracts. Cancer Epidemiol. Biomarkers Prev., 16(4):847-851,
2007
2897. Aziz MH, Reagan-Sahw S, Wu J, et al. Chemoprevention of skin cancer by grape constituent resveratrol:
relevance to human disease? FASEB J., 19:1193-1195, 2005
2898. De Pierro F, Callegari A, Carotenuto D, et al. Clinical efficacy, safety and tolerability of BIO-C (nicronized
silymarin) as a galactagogue. Acta Biomed., 79(3):205-210, 2008
2899. Turkyilmaz C, Onal E, Hirfanoglu IM, et al. The effect of galactagogue herbal tea on breast milk production
and short-term catch-up of birth weight in the first week of life. J. Altern. Compl. Med., 17(2):139-142,
2011
2900. Deep G, Agarwal R. Chemopreventive efficacy of silymarin in skin and prostate cancer. Integrat. Cancer
Ther., 6(2):130-145, 2007
2901. Song Z, Deaciuc I, Song M, et al. Silymarin protects against acute ethanol-induced hepatotoxicity in mice.
Alcohol. Clin. Exp. Res., 30(3):407-413, 2006
2902. Lewerenz V, Hanelt S, Nastevska C, et al. Antioxidants protect primary rat hepatocyte cultures against
acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. Toxicol.,
191:179-187, 2003
2903. Ramadan LA, Roushdy HM, Abu Senna GM, et al. Radioprotective effect of silymarin against radiation
induced hepatotoxicity. Pharmacol. Res., 45(6):447-454, 2002
133
2904. Clark CA, McEachem MD, Shah SH, et al. Curcumin inhibits carcinogen and nicotine-induced mammalian
target of rapamycin pathway activation in head and neck squamous cell carcinoma. Cancer Prev. Res.,
3(12):1586-1595, 2010
2905. Kong W-J, Wei J, Zuo Z-Y, et al. Combination of simvastatin with berberine improves the lipid-lowering
efficacy. Metab. Clin. Exp., 57:1029-1037, 2008
2906. Pearson DA, Paglieroni TG, Rein D, et al. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet
function. Thromb. Res., 106:191-197, 2002
2907. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid
berberine. J. Clin. Endocrinol. Metab., 93(7):2559-2565, 2008
2908. Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through
increasing insulin receptor expression. Metabol. Clin. Exp., 59:285-292, 2010
2909. Pillai AK, Sharma KK, Gupta YK, et al. Anti-emetic effect of ginger powder versus placebo as an add-on
therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr. Blood Cancer,
56:234-238, 2011
2910. Chen J-T, Tominaga K, Sato Y, et al. Maitake mushroom (Grifola frondosa) extract induces ovulation in
patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure
with first-line clomiphene citrate. J. Altern. Compl. Med., 16(12):1-5, 2010
2911. Heinrich U, Neukam K, Tronnier H, et al. Long-term ingestion of high flavanol cocoa provides
photoprotection against UV-induced erythema and improves skin condition in women. J. Nutr., 136:1565-
1569, 2006
2912. Williams S, Tamburic S, Lally C. Eating chocolate can signifcantly protect the skin from UV light. J. Cosm.
Derm., 8:169-173, 2009
2913. Teschke R, Qiu SX, Lebot V. Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and
mould hepatotoxins as primarily assumed culprits. Dig. Liver Dis., 43(9):676-681, 2011
2914. Nandakumar DN, Nagaraj VA, Vathsala PG, et al. Curcumin-artemisinin combination therapy for malaria.
Antimicrob. Agents Chemother., 50(5):1859-1860, 2006
2915. Stavro PM, Woo M, Heim TF, et al. North American ginseng exerts a neutral effect on blood pressure in
individuals with hypertension. Hypertension, 46:406-411, 2005
2916. Barton DL, Soori GS, Bauer BA, et al. Pilot study of Panax quinquefolius (American ginseng) to improve
cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA.
Support. Care Cancer, 18:179-187, 2010
2917. Vuksan V, Sievenpiper JL, Wong J, et al. American ginseng (Panax quinquefolius L.) attenuates postprandial
glycemia in a time-dependent but not dose-dependent manner in healthy individuals. Am. J. Clin. Nutr.,
73:753-758, 2001
2918. McElhaney JE, Gravenstein S, Cole SK, et al. A placebo-controlled trial of a proprietary extract of North
American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J. Am.
Geriatr. Soc., 52:13-19, 2004
2919. McElhaney JE, Goel V, Toane B, et al. Efficacy of COLD-fX in the prevention of respiratory symptoms in
community-dwelling adults: a randomized, double-blinded, placebo controlled trial. J. Altern. Compl. Med.,
12(2):153-157, 2006
2920. de Oliveira Campos MP, Riechelmann R, Martins LC, et al. Guarana (Paullinia cupana) improves fatigue in
breast cancer patients undergiong systemic chemotherapy. J. Altern. Compl. Med., 17(6):505-512, 2011
2921. da Costa Miranda V, Trufelli DC, Santos J, et al. Effectiveness of guarana (Paullinia cupana) for
postradiation fatigue and depression: results of a pilot double-blind randomized study. J. Altern Compl.
Med., 15(4):431-433, 2009
2922. Pawar AA, Tripathi DN, Ramarao, et al. Protective effects of American ginseng (Panax quinequefolium)
against mitomycin C induced micronuclei in mice. Phytother. Res., 21:1221-1227, 2007
2923. Li B, Wang C-Z, He T-C, et al. Antioxidants potentiate American ginseng-induced killing of colorectal cancer
cells. Cancer Lett., 289)1):62-70, 2010
2924. Xu T-M, Xin Y, Cui M-H, et al. Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on
growth and angiogenesis of ovarian cancer. Chin. Med. J., 120(7):584-588, 2007
2925. Zhang QH, Wu CF, Duan L, et al. Protective effects of ginsenoside Rg 3 against cyclophosphamide-induced
DNA damage and cell apoptosis in mice. Arch. Toxicol., 82:117-123, 2008
2926. Wang Z, Zheng Q, Liu K, et al. Ginsenoside Rh2 enhances antitumour activity and decreases genotoxic effect
of cyclophosphamide. Bas. Clin. Pharmacol., 98:411-415, 2006
134
2927. Li X-L, Wang C-Z, Sun S, et al. American ginseng berry enhances chemopreventive effect of 5-FU on human
colorectal cancer cells. Oncol. Rep., 22:943-952, 2009
2928. Li J, Ichikawa T, Jin Y, et al. An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions
in cardiomyocytes. J. Ethnopharmacol., 130:222-230, 2010
2929. Kim H-S, Hong Y-T, Oh K-W, et al. Inhibition by ginsenosides Rb1 and Rg1 of methamphetamine-induced
hyperactivity, conditioned place preference and postsynaptic dopamine receptor supersensitivity in mice.
Gen. Pharmac., 30(5):783-789, 1998
2930. Shin E-J, Nabeshima T, Suh H-W, et al. Ginsenosides attenuate methamphetamine-induced behavioral side
effects in mice via activation of adenosine A2A receptors: possible involvements of the striatal reduction in
AP-1 DNA binding activity and proenkephalin gene expression. Behav. Brain Res., 158:143-157, 2005
2931. Kim H-S, Kim K-S, Oh K-W. Inhibition by ginsenosides Rb1 and Rg1 of cocaine-induced hyperactivity,
conditioned place preference, and postsynaptic dopamine receptor supersensitivity in mice. Pharmacol.
Biochem. Behav., 63(3):407-412, 1999
2932. Jia X, Chen Y, Zidichouski J, et al. Co-administration of berberine and plant stanols synergistically reduces
plasma cholesterol in rats. Atheroscler., 201:101-107, 2008
2933. Wang Y, Jia X, Ghanam K, et al. Berberine and plant stanols synergistically inhibit cholesterol absorption in
hamsters. Atheroscler., 209:111-117, 2010
2934. Gaona-Gaona L, Molina-Jijon EM, Tapia E, et al. Protective effect of sulforaphane pretreatment against
cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicol., 286:20-27, 2011
2935. Lambert JD, Hong J, Kim DH, et al. Piperine enhances the bioavailability of the tea polyphenol (−)-
epigallocatechin-3-gallate in mice. J. Nutr., 134:1948-1952, 2004
2936. Rastogi R, Saksena S, Garg NK, et al. Picroliv protects against alcohol-induced chronic hepatotoxicity in rats.
Planta Med., 62(3):283-285, 1996
2937. Dwivedi V, Khan A, Vasco A, et al. Immunomodulator effect of Picroliv and its potential in treatment against
resistant Plasmodium yoelii (MDR) infection in mice. Pharm. Res., 25(10):2312-2319, 2008
2938. Appiah-Opong R, Commandeur JNM, van Vugt-Lussenburg B, et al. Inhibition of human recombinant
cytochrome P450s by curcumin and curcumin decomposition products. Toxicol., 235:83-91, 2007
2939. Gibbons CH, Wang N, Freeman R. Capsaicin induces degeneration of cutaneous autonomic nerve fibers. Ann.
Neurol., 68:888-898, 2010
2940. Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled
trial. Can. Med. Assoc. J., 182(14):E694-E701, 2010
2941. Engels FK, de Jong FA, Sparreboom A, et al. Medicinal cannabis does not influence the clinical
pharmacokinetics of irinotecan and docetaxel. Oncologist., 12:291-300, 2007
2942. Chang AE, Shiling DJ, Stillman RC, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients
receiving high-dose methotrexate. Ann. Int. Med., 91:819-824, 1979
2943. Chang AE, Shiling DJ, Stillman RC, et al. A prospective evaluation of delta-9-tetrahydrocannabinol as an
antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer, 47:1746-1751, 1981
2944. Amar MB. Cannabinoids in medicine: a review of their therapeutic potential. J. Ethnopharm., 105:1-25, 2006
2945. Chearwae W, Wu C-P, Chu H-Y, et al. Curcuminoids purified from turmeric powder modulate the function of
human multidrug resistance protein 1 (ABCC1). Cancer Chemother. Pharmacol., 57:376-388, 2006
2946. Iwata H, Tezuka Y, Kadota S, et al. Identification and characterization of potent CYP3A4 inhibitors in
schisandra fruit extract. Drug Metab. Dispos., 32(12):1351-1358, 2004
2947. Jang E-H, Park Y-C, Chung W-G. Effects of dietary supplements on induction and inhibition of cytochrome
P450s protein expression in rats. Food Chem Toxicol., 42:1749-1756, 2004
2948. Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor
receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell
carcinoma cell lines. Clin. Cancer Res., 7:4220-4229, 2001
2949. Sugiyama T, Sadzuka Y, Tanaka K, et al. Inhibition of glutamate transporter by theanine enhances the
therapeutic efficacy of doxorubicin. Toxicol. Lett., 121:89-96, 2001
2950. Kim SH, Hong KO, Chung W-Y, et al. Abrogation of cisplatin-induced hepatotoxicity in mice by
xanthorrhizol is related to its effect on the regulation of gene transcription. Toxicol. Appl. Pharmacol.,
196:346-355, 2004
2951. Farid R, Rezaieyazdi Z, Mirfeizi Z, et al. Oral intake of purple passion fruit peel extract reduces pain and
stiffness and improves physical function in adult patients with knee osteoarthritis. Nutrit. Res., 30:601-606,
2010
135
2952. Maluf E, Barros HMT, Frochtengarten ML, et al. Assessment of the hypnotic/sedative effects and toxicity of
Passiflora edulis aqueous extract in rodents and humans. Phytother. Res., 5:262-266, 1991
2953. Tan PV, Nyasse B, Dimo T, et al. Gastric cytoprotective anti-ulcer effects of the leaf methanol extract of
Ocimum suave (Lamiaceae) in rats. J. Ethnopharm., 82:69-74, 2002
2954. Zheng G-Q, Kenney PM, Lam LKT. Sequiterpenes from clove (Eugenia caryophyllata) as potential
anticarcinogenic agents. J. Nat. Prod., 55(7):999-1003, 1992
2955. Benencia F, Courreges MC. In vitro and in vivo activity of eugenol on human herpesvirus. Phytother. Res.,
14:495-500, 2000
2956. Hemaiswarya S, Doble M. Synergistic interaction of eugenol with antibiotics against Gram negative bacteria.
Phytomed., 16:997-1005, 2009
2957. Morsy MA, Fouad AA. Mechanisms of gastroprotective effect of eugenol in indomethacin-induced ulcer in
rats. Phytother. Res., 22:1361-1366, 2008
2958. Casasso R, Pinto L, Vuotto ML, et al. Preventive effect of eugenol on PAF and ethanol-induced gastric
mucosal damage. Fitoterapia, 71:S131-S137, 2000
2959. Kumaravelu P, Dakshinamoorthy DP, Subramaniam S, et al. Effect of eugenol on drug-metabolizing enzymes
of carbon tetrachloride-intoxicated rat liver. Biochem. Pharmacol., 49(11):1703-1707, 1995
2960. Chan ALF, Leung HWC, Wu J-W, et al. Risk of hemorrhage associated with co-prescriptions for Ginkgo
biloba and antiplatelet or anticoagularnt drugs. J. Altern. Compl. Med., 17(6):513-517, 2011
2961. Bijak M Bobrowski M, Borowiecka M, et al. Anticoagulant effect of polyphenols-rich extracts from black
chokeberry and grape seeds. Fitoterapia, 82:811-817, 2011
2962. Willich SN, Rossnagel K, Roll S, et al. Rose hip herbal remedy in patients with rheumatoid arthritis - a
randomised controlled trial. Phytomed., 17(2):87-93, 2010
2963. Deng JW, Shon J-H, Shin H-J, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin.
Pharm. Res., 25(8):1807-1814, 2008
2964. Ryszawa N, Kawczynska-Drozdz A, Pryjma J, et al. Effects of novel plant antioxidants on platelet superoxide
production and aggregation in atherosclerosis. J. Physiol. Pharmacol., 57:611-626, 2006
2965. Malati CY, Robertson SM, Hunt JD, et al. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-
glycoprotein (P-gp) activity in healthy participants. J. CLin. Pharmacol., [epub ahead of print doi:
10.1177/0091270011407194] 2011
2966. Steigerwalt RD Jr, Belcar G, Morazzoni P, et al. Mirtogenol ® potentiates latanoprost in lowering intraocular
pressure and improves ocular blood flow in asymptomatic subjects. Clin. Ophthamol., 4:471-476, 2010
2967. Capasso R, Aviello G, Capasso F, et al. Silymarin BIO-C®, and extract from Silybum marianum fruits,
induces hyperprolactinemia in intact female rats. Phytomed., 16:839-844, 2009
2968. Cho Y-S, Oh JJ, Oh K-H. Synergistic anti-bacterial and proteomic effects of epigallocatechin gallate on
clinical isolates of imipenem-resistant Klebsiella pneumoniae. Phytomed., 18:941-946, 2011
2969. Kuepper R, van Os J, Lieb R, et al. Continued cannabis use and risk of incidence and persistence of psychotic
symptoms: 10 year follow-up cohort study. Br. Med. J., 342:d738[Epub ahead of print], 2011
2970. Chow H-HS, Garland LL, Hsu C-H, et al. Reveratrol modulates drug- and carcinogen-metabolizing enzymes
in a healthy volunteer study. Cancer Prev. Res., 3(9):1168-1175, 2010
2971. Cuendet M, Oteham CP, Moon RC, et al. Quinone reductase induction as a biomarker for cancer
chemoprevention. J. Nat. Prod., 69:460-463, 2006
2972. Queenan KM, Stewart ML, Smith KN, et al. Concentrated oat -glucan, a fermentable fiber, lowers serum
cholesterol in hypercholesterolemic adults in a randomized controlled trial. Nutrit. J., 6:6, 2007
2973. Ren Y, Whittard J, Higuera-Matas A, et al. Cannabidiol, a nonpsychotropic component of cannabis, inhibits
cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J. Neurosci.,
29(47):14764-14769, 2009
2974. Zaidan MRS, Noor Rain A, Badrul AR, et al. In vitro screening of five local medicinal plants for antibacterial
activity using disc diffusion method. Trop. Biomed., 22(2):165-170, 2005
2975. Jarukamjorn K, Don-in K, Makejaruskul C, et al. Impact of Andrographis paniculata crude extract on mouse
hepatic cytochrome P450 enzymes. J. Ethnopharm., 105:464-467, 2006
2976. Mukherjee M Bhaskaran N, Srinath R, et al. Anti-ulcer and antioxidant activity of GutGard™. Ind. J. Exp.
Biol., 48:269-274, 2010
2977. Parker LA, Burton P, Sorge RE, et al. Effect of low doses of 9-tetrahydrocannabinol and cannabidiol on the
extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats.
Psychopharm., 175:360-366, 2004
136
2978. Mrozikiewicz PM, Bogacz A, Karasiewicz M, et al. The effect of standardized Echinacea purpurea extract on
rat cytochrome P450 expression level. Phytomed., 17:830-833, 2010
2979. Wojcikowski K, Wohlmuth H, Johnson DW, et al. Dioscorea villosa (wild yam) induces chronic kidney
injury via pro-fibrotic pathways. Fd. Chem. Toxicol., 46:3122-3131, 2008
2980. Brantley SJ, Oberlies NH, Kroll DJ, et al. Two flavonolignans from milk thistle (Silybum marianum) inhibit
CYP2C9-mediated warfarin metabolism at clinically achievable concentrations.l J. Pharm. Exp. Ther.,
332(8):1081-1087, 2010
2981. Han Y, Guo D, Chen Y, et al. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite
E-3174 in healthy Chinese volunteers. Eur. J. Clin. Pharmacol., 65:585-591, 2009
2982. Yarnell E, Abascal K. Nigella sativa holy herb of the Middle East. Altern. Compl. Ther., 17(2):99-105, 2011
2983. Nagi MN, Almakki HA, Sayed-Ahmed MM, et al. Thymoquinone supplementation reverses acetaminophen-
induced oxidative stress, nitric oxide production, and energy decline in mice liver. Food Chem Toxicol.,
48:23-61-2365, 2010
2084. El-Dakkakhny M, Barakat M, El-Halim MA, et al. Effects of Nigella sativa oil on gastric secretion and
ethanol induced ulcer in rats. J. Ethnopharm., 72:299-304, 2000
2985. Banerjee S, Kaseb AO Wang Z, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by
thymoquinone in pancreatic cancer. Cancer Res., 69(13):5575-5583, 2009
2986. Psaltopoulou T, Kosti RI, Haidopoulos D, et al. Olive oil intake is inversely related to cancer prevalence: A
systematic review and a meta-analysis of 13800 patients and 23340 controls in 19 observational studies.
Lipids Health Dis., 10:127, 2011
2987. Arslan SO, Gelir E, Armutcu F, et al. The protective effect of thymoquinone on ethanol-induced acute gastric
damage in the rat. Nutrit. Res., 25:673-680, 2005
2988. Boskabady MH, Javan H, Sajady M, et al. The possible prophylactic effect of Nigella sativa seed extract in
asthmatic patients. Fund. Clin. Pharmacol., 21:559-566, 2007
2989. Boskabady MH, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic
patients. Phytomed., 17:707-713, 2010
2990. Li J, Seibold P, Chang-Claude J, et al. Coffee consumption modifies risk of estrogen-receptor negative breast
cancer. Breast Cancer Res., 13:R49, 2011
2991. Larsson SC, Wolk A. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterol., 132:1740-
1745, 2007
2992. Holick CN, Smith SG, Giovannucci E, et al. Coffee, tea, caffeine intake, and risk of adult glioma in three
prospective cohort studies. Cancer Epidemiol. Biomarkers. Prev., 19(1):39-47, 2010
2993. Michaud DS, Gallo V, Schlehofer B, et al. Coffee and tea intake and risk of brain tumors in the European
Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am. J. Clin. Nutr., 92:1145-1150,
2010
2994. Nasr A, Hafeh H. Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total
hepatic perfusion and liver functions. Fertil. Steril., 92(5):1780-1782, 2009
2995. Adhvaryu MR, Reddy NM, Vakharia BC. Prevention of hepatotoxicity due to antituberculosis treatment: A
novel integrative approach. World J. Gastroenterol., 14(30):4753-4762, 2008
2996. Dougherty U, Mustafi R, Wang Y, et al. American ginseng suppresses Western diet-promoted tumorigenesis
in model of inflammation-associated colon cancer: role of EGFR. BMC Compl. Altern. Med., 11:111, 2011
2997. Stoner GD, Dombkowski AA, Reen RK, et al. Carcinogen-altered genes in rat esophagus positively
modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate. Cancer
Res., 68(15):6460-6467, 2008
2998. Domola MS, Vu V, Robson-Doucette CA, et al. Insulin mimetics in Urtica dioica: Structural and
computational analyses of Urtica dioica extracts. Phytother. Res., 24:S175-S182, 2010
2999. Weng C-J, Yen G-C. The in vitro and in vivo experimental evidences disclose the chemopreventive effects of
Ganoderma lucidum on cancer invasion and metastasis. Clin. Exp. Metastasis, 27:361-369, 2010
3000. Goel HC, Bala M. Seabuckthorn. (Hippophae rhamnoides) as a radio-protector. In: Seabuckthorn (Hippophae
L.): A Multipurpose Wonder Plant, vol. 2; Singh V, ed., Daya Pub. House, New Delhi, India; pp. 419-455,
2005
3001. Filip GA, Clichici S. Chemoprevention of skin cancer by natural compounds. In: Skin Cancers - Risk Factors,
Prevention and Therapy, La Porta CAM, ed.; InTech open access book, www.intechopen.com, Nov., 2011
3002. Tao Y, Pinzon-Arango PA, Howell AB, et al. Oral consumption of cranberry juice cocktail inhibits molecular-
scale adhesion of clinical uropathogenic Eschericia coli. J. Med. Food, 14(7/8):739-745, 2011
137
3003. Katiyar SK, Mukhtar H. Green tea polyphenol (−)-epigallocatechin-3-gallate treatment to mouse skin prevents
UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress. J.
Leukoc. Biol., 69:719-726,2001
3004. Lu Y-P, Lou Y-R, Li XH, et al. Stimulatory effect of oral administration of green tea or caffeine on ultraviolet
light-induced increases in epidermal wild-type p53, p21(WAF1/CIP1), and apoptotic sunburn cells in SKH-
1 mice. Cancer Res., 60:4785-4791, 2000
3005. Prakash J, Gupta SK, Dinnda AK. Withania somnifera root extract prevents DMBA-induced squamous cell
carcinoma of skin in Swiss albino mice. Nutrit. Cancer, 42(1):91-97, 2002 3006.
3006. Afaq F, Malik A, Syed D, et al. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of
mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal
keratinocytes. Photochem. Photobiol., 81:38-45, 2005
3007. Afaq F, Syed DN, Malik A, et al. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects
human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. J.
Invest. Derm., 127:222-232, 2007
3008. Ahsan H, Reagan-Shaw S, Eggert DM, et al. Protective effect of sanguinarine on ultraviolet B-mediated
damages in SKH-1 hairless house skin: implications for prevention of skin cancer. Photochem. Photobiol.,
83:986-993, 2007
3009. Svobodova A, Zdarilova A, Walterova D, et al. Flavonolignans from Silybum marianum moderate UVA-
induced oxidative damage to HaCaT keratinocytes. J. Dermatol. Sci., 48:213-224, 2007
3010. Gu M, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits ultraviolet B radiation-induced mitogenic and
survival signaling, and associated biological responses in SKH-1 mouse skin. Carcinogen., 26(8):1404-
1413, 2005
3011. Dhanalakshmi S, Mallikarjuna GU, Singh RP, et al. Silibinin prevents ultraviolet radiation-caused skin
damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of
p53-p21/Cip1 in epidermis. Carcinogen., 25(8):1459-1465, 2004
3012. Kim J-K, Kim Y, Na K-M, et al. [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression
in vitro and in vivo. Free Rad. Res., 41(5):603-614, 2007
3013. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John's wort despite
hormonal contraception. Br. J. Clin. Pharmacol., 55:112-113, 2003
3014. Singh A, Singh SP, Bamezai R. Modulatory potential of clocimum oil on mouse skin papillomagenesis and
the xenobiotic detoxication system. Food Chem. Toxicol., 37:663-670, 1999
3015. Prashar R, Kumar A, Banerjee S, et al. Chemopreventive action by an extract from Ocimum sanctum on
mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid
soluble sulfydryl level. Anti-Cancer Drugs, 5:567-572, 1994
3016. Filip A, Daicoviciu D, Clichici S, et al. Photoprotective effects of two natural products on ultravioletB-
induced oxidative stress and apoptosis in SKH-1 mouse skin. J. Med. Food, 14(7/8):761-766, 2011
3017. Wang Y, Yaping E, Xhang X, et al. Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in
vivo by a tyrosine kinase inhibitor genistein. Carcinogen., 19(4):649-654, 1998
3018. Wei H, Zhang X, Wang Y, et al. Inhibition of ultraviolet light-induced oxidative events in the skin and
internal organs of hairles mice by isoflavone genistein. Cancer Lett., 185:21-29, 2002
3019. Khan MR, Badar I, Siddiquah A. Prevention of hepatorenal toxicity with Sonchus asper in gentamicin treated
rats. BMC Compl. Altern. Med., 11:113, 2011
3020. Fankam G, Jeuete V, Voukeng IK, et al. Antibacterial activities of selected Cameroonian spices and their
synergistic effects with antibiotics against multidrug-resistant phenotypes. BMC Compl. Altern. Med.,
11:104, 2011
3021. Methlie P, Husebye EES, Hustad S, et al. Grapefruit juice and licorice increase cortisol availability in patients
with Addison's disease. Eur. J. Endocrin., 165:761-769, 2011
3022. Diederich S, Quinkler M, Burkhardt P, et al. 11-Hydroxysteroid-dehydrogenase isoforms: tissue disribution
and implications for clinical medicine. Eur. J. Clin. Invest., 30(Suppl. 3):21-27, 2000
3023. Budnitz DS, Lovegrove, Shehab N, et al. Emergency hospitalizations for adverse drug events in older
Americans. New Engl. J. Med., 365(21):2002-2012, 2011
3024. Balbir-Gurman A, Fuhrman B, Braun-Moscovici Y, et al. Consumption of pomegranate decreases serum
oxidative stress and reduces diseasae activity in patients with active rheumatoid arthritis: a pilot study.
I.M.A.J., 13:474-479, 2011
138
3025. Schrieber SJ, Wen Z, Vourvahis M, et al. The pharmacokinetics of silymarin is altered in patients with
hepatitis C virus and nonalcoholic fatty liver disease and correlates with plasma caspase-3/7 activity. Drug
Metab. Dispos., 36(9):1909-1916, 2008
3026. Schrieber SJ, Hawke RL, Wen Z, et al. Differences in the disposition of silymarin between patients with non-
alcoholic fatty liver disease and chronic hepatitis C. Drug Metab. Dispos., online prepub.
doi:10:10.1124/dmd.111.040212, Aug. 24, 2011
3027. Leung H, Hung A, Hui ACF, et al. Warfarin overdose due to the possible effects of Lycium barbarum L. Food
Chem. Toxicol., 46:1860-1862, 2008
3028. Reeve VE, Allanson M, Arun SJ, et al. Mice drinking goji berry juice (Lycium barbarum) are protected from
UV radiation-induced skin damage via antioxidant pathways. Photochem. Photobiol. Sci., 9:601-607, 2010
3029. Xin Y-F, Zhou G-L, Deng Z-Y, et al. Protective effect of Lycium barbarum on doxorubicin-induced
cardiotoxicity. Phytother. Res., 21:1020-1024, 2007
3030. Gong H-Y, Shen P, Jin L, et al. Therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin
C (MMC)-induced myelosuppressive mice. J. Exp. Ther. Oncol., 4:181-187, 2004 \3031.
3031. Vuuren S van, Viljoen A. Plant-based antimicrobial studies − methods and approaches to study the interaction
between natural products. Planta Med., 77:1168-1182, 2011
3032. Fukai T, Oku Y, Hano Y, et al. Antimicrobial activities of hydrophobic 2-arylbenzofurans and an isoflavone
against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Planta med.,
70:685-687, 2004
3033. Al-hebshi N, Al-haroni M, Skaug N. In vitro antimicrobial and resistance-modifying activities of aqueous
crude khat extracts against oral microorganisms. Arch. Oral Biol., 51:183-188, 2006
3034. Ibezin EC, Esimone CO, Nnamani PO, et al. In vitro study of the interaction between some fluoroquinolones
and extract of Kola nitida seed. Afr. J. Biotech., 5(19):1781-1784, 2006
3035. Filoche SK, Soma K, Sisson s CH. Antimicrobial effects of essential oils in combination with chlorhexidine
digluconate. Oral Microb. Immunol., 20:221-225, 2005
3036. Walencka E, Roxalska S, Wysokinska H, et al. Salvipisone and aethiopinone from Salvia sclarea hairy roots
modulate staphylococcal antibiotic resistance and express anti-biofilm activity. Planta Med., 73:545-551,
2007
3037. Dinkova-Kostova AT, Jenkins SN, Fahey JW, et al. Protection against UV-ligh-induced skin carcinogenesis in
SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett., 240:243-252,
2006
3038. Lee YS, Han CH, Kang SH, et al. Synergistic effect between catechin and ciprofloxacin on chronic bacterial
prostatitis rat model. Int. J. Urol., 12:383-389, 2005
3039. Lee Y-S, Kang O-H, Choi J-G, et al. Synergistic effects of the combinaton of galangin with gentamicin
against methicillin-resistant Staphylococcus aureus. J. Microbiol., 46(3):283-288, 2008
3040. D'Arrigo M, Ginestra G, Mandalari G, et al. Synergism and postantibiotic effect of tobramycin and Melaleuca
alternifolia (tea tree) oil against Staphylococcus aureus and Escherichia coli. Phytomed., 17:317-322, 2010
3041. Rosato A, Vitali C, De Laurentis N, et al. Antibacterial effect of some essential oils administered alone or in
combination with norfloxacin. Phytomed., 14:727-732, 2007
3042. Schelz Z, Molnar J, Hohmann J. Antimicrobial and antiplasmid activities of essential oils. Fitoterapia,
77:279-285, 2006
3043. Yeung JHK, Or PMY. Polysaccharide peptides from Coriolus versicolor competitively inhibit tolbutamide 4-
hydroxylation in specific human CYP2C9 isoform and pooled human liver microsomes. Phytomed.,
18:1170-1175, 2011
3044. Li L, Stanton JD, Tolson AH, et al. Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the
expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane
receptor, and aryl hydrocarbon receptor-mediated pathways. Pharm. Res., 26(4):872-882, 2009
3045. Na DH, Ji HY, Park EJ, et al. Evaluation of metabolism-mediated herb-drug interactions. Arch. Pharm. Res.,
34(11):1829-1842, 2011
3046. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against
multi-drug resistant Salmonella typhi. Phytother. Res., 18:670-673, 2004
3047. Palaniappan K, Holley RA. Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant
bacteria. Int. J. Food Microb., 140:164-168, 2010
3048. Hemaiswarya S, Kruthiventi AK, Doble M. Synergism between natural products and antibiotics against
infectious diseases. Phytomed., 15:639-652, 2008
139
3049. Endo EH, Cortez DAG, Ueda-Nakamura T, et al. Potent antifungal activity of extracts and pure compound
isolated from pomegranate peels and synergism with fluconazole against Candida albicans. Res.
Microbiol., 161:534-540, 2010
3050. Shin S, Anti-Aspergillus activities of plant essential oils and their combination effects with ketoconazole or
amphotericin B. Arch. Pharm. Res., 26(5):389-393, 2003
3051. Shin S, Kang C-A. Antifungal activity of the essential oil of Agastache rugosa Kuntze and its synergism with
ketoconazole. Lett. Appl. Microbiol., 36:111-115, 2003
3052. Rosato A, Vitali C, Gallo D, et al. The inhibition of Candida species by selected essential oils and their
synergism with amphotericin B. Phytomed., 15:635-638, 2008
3053. Rosato A, Vitali C, Piarulli M, et al. In vitro synergic efficacy of the combination of Nystatin with the
essential oils of Origanum vulgare and Pelargonium graveolens against some Candida species. Phytomed.,
16:972-975, 2009
3054. Suresh B, Sriram S, Dhanaraj SA, et al. Anticandidal activity of Santolina chamecyparissus volatile oil. J.
Ethnopharm., 55:151-159, 1997
3055. Giordani R, Trebaux J, Masi M, et al. Enhanced antifungal activity of ketoconazole by Euphorbia characias
latex against Candida albicans. J. Ethnopharm., 78:1-5, 2001
3056. Chan WY, Tam PPL, Yeung HW. The termination of early pregnancy in the mouse by -momorcharin.
Contracept., 29(1):91-100, 1984
3057. Chan WY, Tam PPL So KC, et al. The inhibitory effects of -momorcharin on endometrial cells in the mouse.
Contracept., 31(1):83-90, 1985
3058. Chan WY, Tam PPL Choi HL, et al. Effects of momorcharins on the mouse embryo at the early organogenesis
stage. Contracept., 34(5):537-544, 1986
3059. Heo J-H, Lee S-T, Chu K, et al. An open-label trial of Korean red ginseng as an adjuvant treatment for
congnitive impairment in patients with Alzheimer's disease. Eur. J. Neurol., 15:865-868, 2008
3060. Lee S-T, Chu K, Sim J-Y, et al. Panax ginseng enhances cognitive performance in Alzheimer disease.
Alzheimer Dis. Assoc. Disord., 22(3):222-226, 2008
3061. Wang C-Z, Aung HH, Zhang B, et al. Chemopreventive effects of heat-processed Panax quinquefolius root on
human breast cancer cells. Anticancer Res., 28(5A):2545-2551, 2008
3062. Peralta EA, Murphy LL, Minnis J, et al. American ginseng inhibits induced COX-2 and NFKB activation in
breast cancer cells. J. Surg. Res., 157:261-267, 2009
3063. Corbit R, Ebbs, S, King ML, et al. The influence of lead and arsenite on the inhibition of human breast cancer
MCF-7 cell proliferation by American ginseng root (Panax quinquefolius L.). Life Sci., 78:1336-1340,
2006
3064. Zhang QH, Wu CF, Yang JY, et al. Reduction of cyclophosphamide-induced DNA damage and apoptosis
effects of ginsenoside Rb1 on mouse bone marrow cells and peripheral blood leukocytes. Environ. Toxicol.
Pharmacol., 27:384-389, 2009
3065. Lee T-K, Wang W, O'Brien KF, et al. Effect of North American ginseng on 137Cs-induced micronuclei in
human lymphocytes: a comparison with WR-1065. Phytother. Res., 22:1614-1622, 2008
3066. Lee T-K, O'Brien KF, Wang W, et al. Radioprotective effect of American ginseng on human lymphocytes at
90 minutes postirradiation: a study of 40 cases. J. Altern. Compl. Med., 16(5):561-567, 2010
3067. Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific
kava paradox hypothesis revisited. Br. J. Clin. Pharmacol., 73(2):170-174, 2012
3068. Imanaga J, Kotegawa T, Imai H, et al. The effects of the SLCO2B1 c.1457C>T polymorphism and apple juice
on the pharmacokinetics of fexofenadine and midazolam in humans. Pharmacogen. Genomics, 21:84-93,
2011
3069. Tapaninen T, Neuvonen PJ, Niemi M. Orange and apple juice greatly reduce the plasma concentrations of the
OATP2B1 substrate aliskiren. Br. J. Clin. Pharmacol., 71(5):718-726, 2011
3070. Wang S-S, Dombkowski AA, Seguin C, et al. Mechanistic basis for the chemopreventive effects of black
raspberries at a late stage of rat esophageal carcinogenesis. Mol. Carcinogen., 50:291-300, 2011
3071. Zikri NN, Riedl KM, Wang L-S, et al. Black raspberry components inhibit proliferation, induce apoptosis and
modulate gene expression in rat esophageal epithelial cells. Nutr. Cancer, 61(6):816-826, 2009
3072. Wang L-S, Hecht SS, Carmella SG, et al. Anthocyanins in black raspberries prevent esophageal tumors in
rats. Cancer Prev. Res., 2(1):84-93, 2009
3073. Duncan FJ, Martin JR, Wulff BC, et al. Topical treatment with black raspberry extract reduces cutaneous
UVB-induced carcinogenesis and inflammation. Cancer Prev. Res., 2(7):665-672, 2009
140
3074. Zhang Z, Knobloch TJ, Seamon LG, et al. A black raspberry extract inhibits proliferation and regulates
apoptosis in cervical cancer cells. Gyn. Oncol., 123:401-406, 2011
3075. Bi X, Fang W, Wang L-S, et al. Black raspberries inhibit intestinal tumorigenesis in Apc1638+/- and Muc2-/-
mouse models of colorectal cancer. Cancer Prev. Res., 3(11):1443-1450, 2010
3076. He L, Chen Z, Zhou M, et al. Radix/rhizoma notoginseng extract (Sanchitongtshu) for ischemic stroke: a
randomized controlled study. Phytomed., 18:437-442, 2011
3077. Flammer AJ, Sudano I, Wolfrum M, et al. Cardiovascular effects of flavanol-rich chocolate in patients with
heart failure. Eur. Hear J., [prepublication online doi:10.1093/eurheartj/ehr448] Dec. 15, 2011
3078. Cuzzolin L, Francini-Pesenti F, Verlato G, et al. Use of herbal products among 392 Italian pregnant women:
focus on pregnancy outcome. Pharmacoepidemiol. Drug Safety, 19:1151-1158, 2010
3079. Mohamed M-EF, Fry RF. Inhibitory effects of commonly used herbal extracts on UDP-
glucuronosyltransferase 1A4, 1A6, and 1A9 enzyme activities. Drug Metabol. Dispos., 39(9):1522-1528,
2011
3080. Elberry AA, Abdel-Naim AB, Abdel-Sattar EA, et al. Cranberry (Vaccinium macrocarpon) protects against
doxorubicin-induced cardiotoxicity in rats. Food Chem. Toxicol., 48:1178-1184, 2010
3081. Madhusoodhanan R, Natarajan M, Singh JVN, et al. Effect of black raspberry extract in inhibiting NFkB
dependent radioprotection in human breast cancer cells. Nutrit. Cancer, 62(1):93-104, 2010
3082. Aiyer HS, Gupta RC. Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by
modulating enzymes of estrogen metabolism. Cancer Prev. Res., 3(6):727-737, 2010
3083. Ngo N, Brantley SJ, Carrizosa DR, et al. The warfarin-cranberry interaction revisited: A systematic in vitro-in
vivo evaluation. J. Exp. Pharmacol., 2010(2):83-91, 2010
3084. Iwao K, Kawai RT, Oda M, et al. Physicochemical interactions of metformin hydrochloride and
glibenclamide with several health foods. Yakugaku Zasshi, 128(9):1341-1345, 2008
3085. Ushijima K, Tsuruoka S, Tsuda H, et al. Cranberry juice suppressed the diclofenac metabolism by human
liver microsomes, but not in healthy human subjects. Br. J. Clin. Pharmacol., 68(2):194-200, 2009
3086. Singh AP, Singh RK, Kim KK, et al. Cranberry proanthocyanidins are cytotoxic to human cancer cells and
sensitize platinum-resistant ovarian cancer cells to paraplatin. Phytother. Res., 23(8):1066-1074, 2009
3087. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal plants. Ind. J. Med. Res., 49(1):130-
149, 1961
3088. Paton DM. The contractile response of the isolated rat uterus to noradrenaline and 5-hydroxytryptamine. Eur.
J. Pharmacol., 3:310-315, 1968
3089. Ashraf R, Khan RA, Ashraf I. Garlic (Allium sativum) supplementation with standard antidiabetic agent
provides better diabetic control in type 2 diabetes patients. Pak. J. pharm. Sci., 24(4):565-570, 2011
3090. Kucera M, Kolar P, Barna M, et al. Arnica/hydroxyethyl salicylate combination spray for ankle distortion: a
four-arm randomised double-blind study. Pain Res. Treat., 2011 [7 pp., online pub. article ID 365625, doi:
10.1155/2011/365625]
3091. Zadoyan G, Rokitta D, Klement S, et al. Effect of Ginkgo biloba special extract EGb 761® on human
cytochrome P450 activity: a cocktail interaction study in healthy volunteers. Eur. J. Clin. Pharmacol. [pub.
online, Dec. 21, 2011; doi: 10.1007/s00228-011-1174-5]
3092. Panahi Y, Saadat A, Sahekar A, et al. Effect of ginger on acute and delayed chemotherapy-induced nausea and
vomiting: a pilot, randomized, open-label clinical trial. Integr. Cancer Ther., [online prepub.;
doi:10.1177/1534735411433201] Feb. 7, 2012
3093. Belcaro G, Luzzi R, Di Rocco P, et al. Pycnogenol ® improvements in asthma management. Panmin. Med.,
53(Suppl. 1 to No. 3):57-64, 2011
3094. Lau BHS, Riesen SK, Truong KP, et al. Pycnogenol ® as an adjunct in the management of childhood asthma.
J. Asthma, 41(8):825-832, 2004
3095. Dardano A, Ballardin M, Ferdeghini M, et al. Anticlastogenic effect of Ginkgo biloba extraact in Graves'
disease patients receiving radioiodine therapy. J. Clin. Endocrin. Metab., 92(11):4286-4289, 2007
3096. Dardano A, Ballardin M, Caraccio N, et al. The effect of Ginkgo biloba extract on genotoxic damage in
patients with differentiated thyroid carcinoma receiving thyroid remnant ablation with iodine-131. Thyroid,
22(3):318-324, 2011
3097. Appendino G, Belcaro G, Cornelli U, et al. Potential role of curcumin phytosome (Meriva) in controlling the
evolution of diabetic microangiopathy. A pilot study. Panminerva Med., 53(Suppl. 1-3):1-7, 2011
3098. Lee IT, Chan YC, Lin CW, et al. Effect of cranberry extracts on lipid profiles in subjects with Type 2
diabetes. Diabet. Med., 25:1473-1477, 2008
141
3099. Penzak SR, Robertson SM, Hunt JD, et al. Echinacea purpurea significantly induced cytochrome P450 3A
activity but does not alter lopinavir-ritonavir exposure in healthy subjects. Pharmacother., 30(8):797-805,
2010
3100. Prasain JK, Jones K, Moore R, et al. Effect of cranberry juice concentrate on chemically-induced urinary
bladder cancers. Oncol. Rep., 19(6):1565-1570, 2008
3101. Ren J, Meng S, Lekka CE, et al. Complexation of flavonoids with iron: structure and optical signatures. J.
Phys. Chem. B, 112:1845-1850, 2008
3102. Favela-Hernandex JMJ, Garcia A, Garza-Gonzalez E, et al. Antibacterial and antimycobacterial lignans and
flavonoids from Larrea tridentata. Phytother. Res. [prepub. online; doi:10.1002/ptr.4660], 2012
3103.Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with
active rheumatoid arthritis. Phyother. Res., 26:1719-1725, 2012
3104. Zhou Y, He P, Liu A, et al. Drug-drug interactions between keotconazole and berberine in rats:
pharmacokinetic effects benefit pharmacodynamic synergism. Phytother. Res., 26:772-777, 2012
3105. Qui W, Jiang XH, Liu CX, et al. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-
gp. Phytother. Res., 23:1553-1558, 2009
3106. Iwazaki RS, Endo EH, Ueda-Nakamura T, et al. In vitro antifungal activity of the berberine and its synergism
with fluconazole. Ant. van Leeuwen., 97;201-205, 2010
3107. Han Y, Lee J-H. Berberine synergy with amphotericin B against disseminated candidiasis in mice. Biol.
Pharm. Bull., 28(3):541-544, 2005
3108. Linn Y-C, Lu J, L, Lim L-C, et al. Berberine-induced haemolysis revisited: safety of rhizoma coptidis and
cortex phellodendri in chronic haematological diseases. Phytother. Res., 26:682-686, 2012
3109. Hashem FA, Motawea H, El-Shabrawy AE, et al. Myrosinase hydrolysates of
Brassica oleraceae L. var. italica reduce the risk of colon cancer. Phytother. Res., 26:743-747, 2012
3110. Xin Y-F, You Z-Q, Gao H-Y, et al. Protective effect of Lycium barbarum polysaccharides against
doxorubicin-induced testicular toxicity in rats. Phytother. Res., 26:716-721, 2012
3111. Voruganti S, Yamsani SK, Ravula SK, et al. Effect of pomegranate juice on intestinal transport and
pharmacokinetics of nitrendipine in rats. Phytother. Res. [online prepub.; doi: 10.1002/ptr.3704], 2012
3112. Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and
tolbutamide pharmacokinetics in rats. Drug Metabol. Dispos., 35(2):302-305, 2007
3113. Samojlik I, Petkovic S, Mimica-Dukic N, et al. Acute and chronic pretreatment with essential oil of
peppermint (Mentha x piperita L., Lamiaceae) influences drug effects. Phytother. Res., 26:820-825, 2012
3114. Gheita TA, Kenawy SA. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis
patients: a placebo controlled study. Phytother. Res., 26(8):1246-1248, 2012
3115. Kunnumakkara AB, Diagaradjane P, Anand P, et al. Curcumin sensitized human colorectal cancer to
capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic
mouse model. Int. J. Cancer, 125:2187-2197, 2009
3116. Park J, Ayyappan V, Bae E-K, et al. Curcumin in combination with bortezomib synergistically induced
apoptosis in human multiple myeloma U266 cells. Mol. Oncol., 2:317-326, 2008
3117. Kang HJ, Lee SH, Price JE, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-B in breast
cancer cells and potentiates the growth inhibitory effect of paclitaxel in a breast cancer nude mice model.
Breast J., 15(3):223-229, 2009
3118. Tharakan ST, Inamoto T, Sung B, et al. Curcumin potentiates the antitumor effects of gemcitabine in an
orthotopic model of human bladder cancer through suppression of proliferative and angiogenic biomarkers.
Biochem. Pharmacol., 79:218-228, 2010
3119. Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al. Phase I dose escalation trial of docetaxel plus curcumin
in patients with advanced and metastatic breast cancer. Cancer Biol. Ther., 9(1):8-14, 2010
3120. Epelbaum R, Schaffer M, Vizel B, et al. Curcumin and gemcitabine in patients with advanced pancreatic
cancer. Nutr. Cancer, 62(8):1137-1141, 2010
3121. Akpolat M, Kanter m, Uzal MC. Protective effects of curcumin against gamma radiation-induced ilial
mucosal damage. Arch. Toxicol., 83:609-617, 2009
3122. Cekmen M, Ilbey YO, Ozbeck E, et al. Curcumin prevents oxidative renal damage induced by acetaminophen
in rats. Food Chem. Toxicol., 47:1480-1484, 2009
3123. Blickstein D, Shaklai M, Inbal A. Warfarin antagonism by avocado. Lancet, 337:914-915, 1991
3124. Peynaud D, Charpiat B, Vial T, et al. Tacrolimus severe overdosage after intake of masked grapefruit in
orange marmalade. Eur. J. Clin. Pharmacol., 63:721-722, 2007
142
3125. Ina K, Furuta R, Kataoka T, et al. Lentinan prolonged survival in patients with gastric cancer receiving S-1-
based chemotherapy. World J. Clin. Oncol., 2(10):339-343, 2011
3126. Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction for chronic pain. Clin. Pharmacol.
Ther., 90(6):844-851, 2011
3127. Cho S-M, Shimizu M, Lee CJ, et al. Hypnotic effects and binding studies for GABA A and 5-HT2C receptors of
traditional medicinal plants used in Asia for insomnia. J. Ethnopharm., 132:225-232, 2010
3128. Bijak M, Saluk J, Ponczek MB, et al. Antithrombin effect of polyphenol-rich extracts from black chokeberry
and grape seeds. Phytother. Res. [prepub. online; doi:10.1002.ptr.4682], 2012
3129. Szaefer H, Krajka-Kuzniak V, Bartoszek A, et al. Modulation of carcinogen metabolizing cytochromes P450
in rat liver and kidney by cabbage and sauerkraut juices: comparison with the effects of indole-3-carbinol
and phenethyl isothiocyanate. Phytother. Res. [prepub. online; doi:10.1002/ptr.3692], 2011
3130. Cech NB, Junio HA, Ackermann LW, et al. Quorum quenching and antimicrobial activity of goldenseal
(Hydrastis canadensis) against methicillin-resistant Staphylococcus aureus (MRSA). Planta Med.,
78:1556-1561, 2012
3131. Moussally K, Berard A. Exposure to specific herbal products during pregnancy and the risk of low birth
weight. Altern. Ther., 18(2):36-43, 2012
3132. Kasibhatta R, Naidu MUR. Influence of piperine on the pharmacokinetics of nevirapine under fasting
conditions. Drugs R D. 8(6):383-391, 2007
3133. Lundahl A, Hedeland M, Bondesson U, et al. The effect of St. John's wort on the pharmacokinetics,
metabolism and biliary excretion of finasteride and its metabolites in healthy men. Eur. J. Pharmaceut.
Sci., 36:433-443, 2009
3134. Kim K-A, Park P-W, Park J-Y. Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a
substrate of P-glycoprotein, in healthy volunteers. Eur. J. Clin. Pharmacol., 65:609-614, 2009
3135. Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and
fexofenadine pharmacokinetics in health subjects. Curr. Med. Res. Opion., 24(2):591-599, 2008
3136. Xin H-W, Wu X-C, Li Q, et al. Effects of Schisandra sphenanthera extract on the pharmacokinetics of
midazolam in healthy volunteers. Br. J. Clin. Pharm., 67(5):541-546, 2009
3137. Han Y, Guo D, Chen Y, et al. Effect of continuous silymarin administration on oral talinolol pharmacokinetics
in healthy volunteers. Xenobiot., 39(9):694-699, 2009
3138. Fan L, Mao X-Q, Tao G-Y, et al. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the
pharmacokinetics of talinolol in healthy volunteers. Xenobiot., 39(3):249-254, 2009
3139. Lee SB, Kim CY, Lee HJ, et al. Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma
cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2. Planta Med.,
75:1314-1318, 2009
3140. Demeule M, Brossard M, Turcotte S, et al. Diallyl disulfide, a chemopreventive agent in garlic, induces
multidrug resistance-associated protein 2 expression. Biochem. Biophys. Res. Comm., 324:937-945, 2004
3141. Berginc K, Trontelj J, Kristl A. The influence of aged garlic extract on the uptake of saquinavir and darunavir
into HepG2 cells and rat liver slices. Drug Metab. Pharmacokinet., 25(3):307-313, 2010
3142. Berginc K, Zakelj S, Dristl A. In vitro interactions between aged garlic extract and drugs used for the
treatment of cardiovascular and diabetic patients. Eur. J. Nutr., 49:373-384, 2010
3143. Berginc K, Zakelj S, Ursic D, et al. Aged garlic extract stimulates P-glycoprotein and multidrug resistance
associated protein 2 mediated effluxes. Biol. Pharm. Bull., 32(4):694-699, 2009
3144. Cohen EEW, Wu K, Hartford C, et al. Phase I studies of sirolimus alone or in combination with
pharmacokinetic modulators in advanced cancer patients. Clin. Cancer Res., 18(17):4785-4793, 2012
3145. Zhou Z, Nair MG, Claycombe KJ. Synergistic inhibition of interleukin-6 production in adipose stem cells by
tart cherry anthocyanins and atorvastatin. Phytomed., 19:878-881, 2012
3146. Muthaiyan A, Biswas D, Crandall PG, et al. Application of orange essential oil as an antistaphylococcal agent
in a dressing model. BMC Compl. Altern. Med., 12:125 [doi:10.1186/1472-6882-12-125], 2012
3147. Lucinda LMF, Vieira BJ, Oliveira TT, et al. Evidences of osteoporosis improvement in Wistar rats treated
with Ginkgo biloba extract: a histomorphometric study of mandible and femur. Fitoter., 81:982-987, 2010
3148. Zhao X, Zhang J, Tong N, et al. Berberine attenuates doxorubicin-induced cardiotoxicity in mice. J. Int. Med.
Res., 39:1720-1727, 2011
3149. Shivashankara AR, Azmidah A, Haniadka R, et al. Dietary agents in the prevention of alcohol-induced
hepatotoxicity: preclinical observations. Food Funct., 3:101, 2012
3150. Luczaj W, Skrzydlewska E. Antioxidant properties of black tea in alcohol intoxication. Food Chem. Toxicol.,
42:2045-2051, 2004
143
3151. Das D, Mukherjee S, Mukherjee M, et al. Aqueous extract of black tea (Camellia sinensis) prevent chronic
ethanol toxicity. Curr. Sci., 88(6):952-961, 2005
3152. Padmavathi P, Reddy VD, Varadacharyulu NC. Emblica officinalis protects against alcohol-induced liver
mitochondrial dysfunction in rats. J. Med. Food, 12(2):327-333, 2009
3153. Devipriya N, Sudheer AR, Srinivasan M, et al. Effect of ellagic acid, a plant polyphenol, on fibrotic markers
(MMPs and TIMPs) during alcohol-induced hepatotoxicity. Toxicol. Mech. Meth., 17:349-356, 2007
3154. Devipriya N, Sudheer AR, Menon VP. Dose-response effect of ellagic acid on circulatory antioxidants and
lipids during alcohol-induced toxicity in exprimental rats. Fund. Clin. Pharmacol., 21:621-630, 2007
3155. Devipriya N, Sudheer AR, Vishwanathan P, et al. Modulatory potential of ellagic acid, a natural plant
polyphenol on altered lipid profile and lipid peroxidation status during alcohol-induced toxicity: a
pathohistological study. J. Biochem. Mol. Toxicol., 22(2):101-112, 2008
3156. Kaviarasan S, Sundarapandiyan R, Anuradha CV. Protective action of fenugreek (Trigonella foenum
graecum) seed polyphenols against alcohol-induced protein and lipid damage in rat liver. Cell Biol.
Toxicol., 24:391-400, 2008
3157. Yurt B, Celik I. Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus
armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats. Food Chem. Toxicol., 49:508-
513, 2011
3158. Lin S-C, Lin C-H, Lin C-C, et al. Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by
chronic ethanol consumption and potentiated by carbon tetrachloride. J. Biomed. Sci., 9:401-409, 2002
3159. Nanji AA, Jokelainen K, Tipoe GL, et al. Curcumin prevents alcohol-induced liver disease in rats by
inhibiting the expression of NF-B-dependent genes. Am. J. Physiol. Gastrointest. Liver Physiol.,
284:G321-G327, 2003
3160. Shukla B, Visen PKS, Patnaik GK, et al. Choleretic effect of Picroliv, the hepatoprotective principle of
Picrorhiza kurroa. Planta Med., 57:29-33, 1991
3161. Saraswat B, Visen PKS, Patnaik GK, et al. Hepatoprotective effect of Picroliv against rifampicin-induced
toxicity. Drug Devel. Res., 40:299-303, 1997
3162. Assuncao M, Santos-Marques MJ, Monteiro R, et al. Red wine protects against ethanol-induced oxidative
stress in rat liver. J. Agric. Food Chem., 57:6066-6073, 2009
3163. Kasdallah-Grissa A, Mornagui B, Aouani E, et al. Resveratrol, a red wine polyphenol, attenuates ethanol-
induced oxidative stress in rat liver. Life Sci., 80:1033-1039, 2007
3164. Ajmo JM, Liang X, Rogers CQ, Pennock B, et al. Resveratrol alleviates alcoholic fatty liver in mice. Am. J.
Physiol. Gastrointest. Liver Physiol., 295:G833-G842, 2008
3165. Oliva J, French BA, Li J, et al. Sirt1 involved in energy metabolism: the role of chronic ethanol feeding and
resveratrol. Exp. Mol. Pathol., 85:155-159, 2008
3166. Nencini C, Franchi GG, Cavallo F, et al. Protective effect of Allium neapolitanum Cyr. versus Allium sativum
L. on acute ethanol-induced oxidative stress in rat liver. J. Med. Food, 13(2):329-335, 2010
3167. Hossain S, Chowdhury IH, Basunia MA, et al. Syzygium cumini seed extract protects the liver against lipid
peroxidation with concurrent amelioration of hepatic enzymes and lipid profile of alcoholic rats. J. Compl.
Integr. Med., 8(1):1 [doi: 10.2202/1553-3840.1445k], 2011
3168. Jawanjal H, Pajput MS, Agrawal P, et al. Pharmacological evaluation of fruits of Terminalia belerica Roxb.
for antiulcer activity. J. Compl. Integr. Med., 9(1):9 [doi: 10:1515/1553-3840.1556], 2012
3169. Gupta RL, Jain S, Talwar V, et al. Antitubercular activity of garlic (Allium sativum) extract in combination
with conventional antitubercular drugs in turbercular lymphadenitis. Indian J. Clin. Biochem., 14(1):12-18,
1999
3170. Gupta R, Thakur B, Singh P, et al. Anti-tuberculosis activity of selected medicinal plants against multidrug
resistant Mycobacterium tuberculosis isolates. Indian J. Med. Res., 131:809-813, 2010
3171. Dhamija P, Sethi S, Meharwal S, et al. Crude aqueous extract of garlic reduces MIC of isoniazid and
rifampicin against Mycobacterium tuberculosis by broth microdilution method. J. Compl. Integr. Med.,
7(1):47 [doi: 10.2202/1553-3840.1449], 2010
3172. Murthy PS, Ratnakar P, Gadre DV, et al. Trifluoperazine and DEF-allicin from garlic (Allium sativum) as
potential new antitubercular drugs active against drug resistant Mycobacterium tuberculosis. Indian J. Clin.
Biochem., 12 (Suppl. 1):72-75, 1997
3173. Ramachandran C, Nair SM, Escalon E, et al. Potentiation of etoposide and temozolomide cytotoxicity by
curcumin and Turmeric Force™ in brain tumor cell lines. J. Compl. Integr. Med., 9(1):20 [doi:
10.1515.1553-3840.1614], 2012
144
3174. Ramachandran C, Resek AP, Escalon E, et al. Potentiation of gemcitabine by Turmeric Force™ in pancreatic
cancer cell lines. Oncol. Rep., 23:1529-1535, 2010
3175. Shufelt C, Merz CNB, Yang Y, et al. Red versus white wine as a nutritional aromatase inhibitor in
premenopausal women. J. Womens Health (Larchmont), 21(3):281-284, 2012
3176. Carini M, Aldini G, Orioli M, et al. Antioxidant and photoprotective activity of a lipophilic extract containing
neolignans from Krameria triandra roots. Planta Med., 68:193-197, 2002
3177. Han C, Ding H, Casto B, et al. Inhibition of the growth of premalignant and malignant human oral cell lines
by extracts and components of black raspberries. Nutr. Cancer, 5(2):207-217, 2005
3178. Di Pierro F, Rapacioli G, Ferrara T, et al. Use of a standardized extract from Echinacea angustifolia
(Polinacea®) for the prevention of respiratory tract infections. Altern. Med. Rev., 17(1):36-41, 2012
3179. Kaur G, Jaggi AS, Singh N. Exploring the potential effect of Ocimum sanctum in vincristine-induced
neuropathic pain in rats. J. Brach. Plex. Periph. Nerve Inj., 5:3, 2010
3180. Monga J, Sharma M, Tailor N, et al. Antimelanoma and radioprotective activity of alcoholic aqueous extract
of different species of Ocimum in C57BL mice. Pharmaceut. Biol., 49(4):428-436, 2011
3181. Lahon K, Das S. Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-
induced liver damage in Albino rats. Pharmacog. Res., 3(1):13-18, 2011
3182. Nagaprashantha LD, Vatsyayan R, Singhal J, et al. Anti-cancer effects of novel flavonoid vicenin-2 as a single
agent and in synergistic combination with docetaxel in prostate cancer. Biochem. Pharmacol., 82:1100-
1109, 2011
3183. Mahaprabhu R, Bhandarkar AG, Jangir BL, et al. Ameliorative effect of Ocimum sanctum on meloxicam
induced toxicity in Wistar rats. Toxicol. Int., 18(2):130-136, 2011
3184. Joseph LJ, Bhartiya US, Raut YS, et al. Radioprotective effect of Ocimum sanctum and amifostine on the
salivary gland of rats after therapeutic radioiodine exposure. Cancer Biother. Radiopharm., 26(6):737-743,
2011
3185. Panda VS, Naik SR. Evaluation of cardioprotective activity of Ginkgo biloba and Ocimum sanctum in rodents.
Altern. Med. Rev., 14(2):161-171, 2009
3186. Bhartiyz US, Raut YS, Joseph LJ. Protective effect of Ocimum sanctum L after high-dose 131iodine exposure
in mice: an in vivo study. Indian J. Exp. Biol., 44(8):647-652, 2006
3187. Hussain EH, Jamil K, Rao M. Hypoglycaemic, hypolipidemic and antioxidant properties of tulsi (Ocimum
sanctum Linn) on streptozotocin induced diabetes in rats. Ind. J. Clin. Biochem., 16(2):190-194, 2001
3188. Sethi J, Sood S, Seth S, Taiwar A. Evaluation of hypoglycemic and antioxidant effect of Ocimum sanctum.
Ind. J. Clin. Biochem., 19(2):152-155, 2004
3189. Patil R, Patil R, Ahirwar B, et al. Isolation and characterization of anti-diabetic component (bioactivity-guided
fractionation) from Ocimum sanctum L. (Lamiaceae) aerial part. Asian Pac. J. Trop. Med., 4:278-282, 2011
3190. Blonk M, Colbers A, Poirrters A, et al. Effect of Ginkgo biloba on the pharmacokinetics of raltegravir in
healthy volunteers. Antimicrob. Agents Chemother., 56(10):5070-5075, 2012
3191. Mohamed M-EF, Frye RF. Inhibition of intestinal and hepatic glucuronidation of mycophenolic acid by
Ginkgo biloba extract and flavonoids. Drug Metab. Dispos., 38(2):270-275, 2010
3192. Yang CY, Chao PDL, Hou YC, et al. Marked decrease of cyclosporin bioavailability caused by
coadministration of ginkgo and onion in rats. Food Chem. Toxicol., 44:1572-1578, 2006
3193. Jagetia GC. Radioprotective potential of plants and herbs against the effects of ionizing radiation. J. Clin.
Biochem. Nutr., 40:74-81, 2007
3194. Sunila ES, Kuttan G. Protective effect of Piper longum fruit ethanolic extract on radiation induced damages in
mice: a preliminary study. Fitoter., 76:649-655, 2005
3195. Samarth RM, Goyal PK, Kumar A. Modulation of serum phosphatases activity in Swiss Albino mice against
gamma irradiation by Mentha piperita Linn. Phytother. Res., 16:586-589, 2002
3196. Siddique YH, Ara G, Beg T, et al. Anti-genotoxic effect of Ocimum sanctum L. extract against cyproterone
acetate induced genotoxic damage in cultured mammalian cells. Acta Biol Hung., 58(4):397-409, 2007
3197. Oga EF, Sekine S, Shitara Y, et al. P-glycoprotein mediated efflux in Caco-2 cell monolayers: the influence of
herbals on digoxin transport. J. Ethnopharm., [prepub. online: dx.doi.org/10.1026/j.jep.2012.10.001], 2012
3198. Adhvaryu MR, Reddy N, Parabia MH. Effects of four Indian medicinal herbs on isoniazid-, rifampicin- and
pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs. World J. Gastroenterol.,
13(23):3199-3205, 2007
3199. Manikandan P, Vidjaya Letchoumy P, Prathilba D, et al. Proliferation, angiogenesis and apoptosis-associated
proteins are molecular targets for chemoprevention of MNNG-induced gastric carcinogenesis by ethanolic
Ocimum sanctum leaf extract. Singapore Med. J., 48(7):645-651, 2007
145
3200. Aqil F, Khan MSA, Owais M, et al. Effect of certain bioactive plant extracts on clinical isolates of -
lactamase producing methicillin resistant Staphylococcus aureus. J. Basic Microbiol., 45(2):106-114, 2005
3201. Muto S, Fujita K, Yamazaki Y, et al. Inhibition by green tea catechins of metabolic activation of
procarcinogens by human cytochrome P450. Mut. Res., 479:197-206, 2001
3202. Nishikawa M, Ariyoshi N, Kotani A, et al. Effects of continuous ingestion of green tea or grape seed extracts
on the pharmacokinetics of midazolam. Drug Metab. Pharmacokin., 19(4):280-289, 2004
3203. Zhang Q, Wei D, Liu J. In vivo reversal of doxorubicin resistance by (−)-epigallocatechin gallate in a solid
human carcinoma xenograft. Cancer Lett., 208:179-186, 2004
3204. Farabegoli F, Papi A, Bartolini G, et al. (-)-Epigallocatechin-3-gallate downregulates Pg-; and PCRP in a
tamoxifen resistant MCF-7 cell line. Phytomed., 17:356-362, 2010
3205. Facchinetti F, Pedrielli G, Benoni G, et al. Herbal supplements in pregnancy: unexpected results from a
multicentre study. Hum. Reprod., 27(11):3161-3167, 2012
3206. Shin S-C, Choi J-S. Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of
tamoxifen and its main metabolite, 4-hydroxytamoxifen in rats. Anti-Cancer Drugs, 20:584-588, 2009
3207. Liang G, Tang A, Lin X, et al. Green tea catechins augment the antitumor activity of doxorubicin in an in vivo
model for chemoresistant liver cancer. Int. J. Oncol., 37:111-123, 2010
3208. Chung J-H, Choi D-H, Choi J-S. Effects of oral epigallocatechin gallate on the oral pharmacokinetics of
verapamil in rats. Biopharm. Drug Dispos., 30:90-93, 2009
3209. Choi J-S, Burm J-P. Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats.
Arch. Pharm. Res., 32(12):1721-1725, 2009
3210. Ge J, Tan B-X, Chen Y, et al. Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib:
potential risk of diminished sunitinib bioavailability. J. Mol. Med., 89:595-602, 2011
3211. Torkelson CJ, Sweet E, Martzen MR, et al. Phase 1 clinical trial of Trametes versicolor in women with breast
cancer. ISRN [Int. Schol. Res. Network] Oncol., 2012:#252632[doi:10.5402/2012/251632], 2012
3212. Aruna K, Sivaramakrishnan VM. Anticarcinogenic effects of some Indian plant products. Fd. Chem. Toxic.,
30(11):953-956, 1992
3213. Prashar R, Kumar A, Banerjee S, et al. Chemopreventive action by an extract from Ocimum sanctum on
mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid
soluble sulfydryl level. Anti-Cancer Drugs, 5:567-572, 1994
3214. Ganasoundari A, Zare SM, Uma Devi P. Modification of bone marrow radiosensitivity by medicinal plant
extracts. Br. J. Radiother., 70:599-602, 1997
3215. Uma Devi P, Bisht KS, Vinitha M. A comparative study of radioprotection by Ocimum flavonoids and
synthetic aminothiol protectors in the mouse. Br. J. Radiol., 71:782-784, 1998
3216. Kathikeyan K, Ravichandran P, Govindasamy S. Chemopreventive effect of Ocimum sanctum on DMBA-
induced hamster buccal pouch carcinogenesis. Oral Oncol., 35:112-119, 1999
3217. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of hypoglycaemic activity of some
Indian medicinal plants in alloxan diabetic rats. J. Ethnopharm., 84:105-108, 2003
3218. Dharmani P, Kuchibhotla VK, Maurya R, et al. Evaluation of anti-ulcerogenic and ulcer-healing properties of
Ocimum sanctum Linn. J. Ethnopharm., 93:197-206, 2004
3219. Vats V, Yadav SP, Grover JK. Ethanolic extract of Ocimum sanctum leaves partially attenuates
streptozotocin-induced alterations in glycogen content and carbohydrate metabolism in rats. J.
Ethnopharm., 90:155-160, 2004
3220. Sakina MR, Dandiya PC, Hamdard ME, et al. Preliminary psychopharmacological evaluation of Ocimum
sanctum leaf extract. J. Ethnopharm., 28:143-150, 1990
3221. Penetar DM, Toto LH, Farmer SL, et al. The isoflavone puerarin reduces alcohol intake in heavy drinkers: a
pilot study. Drug Alcohol Depend., 126:251-256, 2012
3222. Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part2): drug interactions involving
popular botancial dietary supplements and their clinical relevance. Planta Med., 78(13):1490-1514, 2012
3223. Hajda J, Rentsch KM, Gubler C, et al. Garlic extract induces intestinal P-glycoprotein, but exhibits no effect
on intestinal and hepatic CYP3A4 in humans. Eur. J. Pharmaceut. Sci., 41:729-735, 2010
3224. Wang X, Wolkoff AW, Morris ME. Flavonoids as a novel class of human organic anion-transporting
polypeptide OATP1B1 (OATP-C) modulators. Drug Metab. Dispos., 33(11):1666-1672, 2005
3225. Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of Ginkgo biloba on the pharmacokinetics of digoxin. Am
J. Ther., 10:247-251, 2003
3226. Liu X-P, Goldring CEP, Wang H-Y, et al. Extract of Ginkgo biloba induces glutathione-S-transferase subunit-
P1 in vitro. Phytomed., 16:451-455, 2009
146
3227. Kim B-H, Kim K-P, Lim KS, et al. Influence of Ginkgo biloba extract on the pharmacodynamic effects and
pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-
sequence, single-dose crossover study in healthy Korean male volunteers. Clin. Ther., 32(2):380-390, 2010
3228. Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and
fexofenadine pharmacokinetics in healthy subjects. Curr. Med. Res. Opin., 24(2):591-599, 2008
3229. Yoshioka M, Ohnishi N, Koishi T, et al. Studies on interactions between functional foods or dietary
supplements and medicines. IV. Effects of Ginkgo biloba leaf extract on the pharmacokinetics and
pharmacodynamics of nifedipine in healthy volunteers. Biol. Pharm. Bull., 27(12):2006-2009, 2004
3230. Lin Y-Y, Chu S-J, Tsai S-H. Association between priapism and concurrent use of risperidone and Ginkgo
biloba. Mayo Clin. Proc., 82(10):1288-1291, 2007
3231. Zhao J, Dasmahapatra AK, Khan SI, et al. Anti-aromatase activity of the constituents from damiana (Turnera
diffusa). J. Ethnopharm., 120:387-393, 2008
3232. Fan L, Zhang W, Guo D, et al. The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin,
substrate of organic anion-transporting polypeptide 1B1. Clin. Pharm. Ther., 83(2):471-476, 2008
3233. Debnath PK, Chattopadhyay J, Mitra A, et al. Adjunct therapy of Ayurvedic medicine with antitubercular
drugs on the therapeutic management of pulmonary tuberculosis. J. Ayur. Integr. Med., 3(3):141-149, 2012
3234. Lukivskaya OY, Naruta E, Sadovnichy V, et al. Reversal of experimental ethanol-induced liver steatosis by
borage oil. Phytother. Res., 26:1626-1631, 2012
3235. Mukherjee S, Dey A, Das T. In vitro antibacterial activity of n-hexane fraction of methanolic extract of
Alstonia scholaris L. R.Br. stem bark against some multidrug resistant human pathogenic bacteria. Eur. J.
Med. Plants, 2(1):1-10, 2012
3236. Ettefagh KA, Burns JT, Junio HA, et al. Goldenseal (Hydrastis canadensis L.) extracts synergistically
enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med., 77:835-840, 2011
3237. Huyen VTT, Phan DV, Thang P, et al. Antidiabetic effects of add-on Gynostemma pentaphyllum extract
therapy with sulfonylureas in type 2 diabetic patients. Evid.-Based Compl. Antern. Med., 2012:#452313, 7
pages [doi: 10.1155/2012/452313]
3238. Guo Y, Chen Y, Tan Z-r, et al. Repeated administration of berberine inhibits cytochromes P450 in
humans. Eur. J. Clin. Pharmacol., 68:213-217, 2012
3239. Sood S, Narang D, Dinda AK, et al. Chronic oral administration of Ocimum sanctum Linn. augments cardiac
endogenous antioxidants and prevents isoproterenol-induced myocardial necrosis in rats. J. Pharm.
Pharmacol., 57:127-133, 2005
3240. van der Logt EMJ, Roelofs HMJ, Nagengast FM, et al. Induction of rat hepatic and intestinal UDP-
glucuronosyltransferases by naturally occurring dietary anticarcinogens. Carcinogen., 24(10):1651-1656,
2003
3241. Mohamed M-EF, Tseng T, Frye RF. Inhibitory effects of commonly used herbal extracts on UGT1A1 enzyme
activity. Xenobiotica, 40(10):663-669, 2010
3242. Williams JA, Ring BJ, Cantrell VE, et al. Differential modulation of UDP-glucuronosyltransferase 1A1
(UGT1A1)-catalyzed estradiol-3-glucuronidation by the addition of UGT1A1 substrates and other
compounds to human liver microsomes. Drug Metab. Dispos., 30:1266-1273, 2002
3243. Fabbriciani G, De Socio GVL. Efavirenz and bone health. AIDS, 23:1181, 2009
3244. Lu T, Sheng H, Wu J, et al. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin
level in Chinese patients with type 2 diabetes. Nutr. Res., 32:408-412, 2012
3245. Hanley MJ, Masse G, Harmatz JS, et al. Pomegranate juice and pomegranate extract do not impair oral
clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin. Pharmacol. Ther.,
92(5):651-657, 2012
3246. Konturek SJ, Brzozowski T, Drozdowicz, et al. Role of leukotrienes and platelet activating factor in acute
gastric mucosal lesions in rats. Eur. J. Pharmacol., 164:285-292, 1989
3247. Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the treatment of painful knee
osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacol., [online prepub.: doi:
10.1007/s10787-012-0163-3], Dec. 16, 2012
3248. Mirzaei MG, Sewell RDE, Kheriri S, et al. A clinical trial of the effect of St. John's wort on migraine
headaches in patients receiving sodium valproate. J. Med. Plants Res., 6(9):1519-1523, 2012
3249. Yang J-F, Yand C-H, Chang H-W, et al. Chemical composition and antibacterial activites of Illicium verum
against antibiotic-resistant pathogens. J. Med. Food, 13(5):1254-1262, 2010
3250. Kim K-J, Yu H-H, Cha J-D, et al. Antibacterial activity of Curcuma longa L. against methicillin-resistant
Staphylococcus aureus. Phytother. Res., 19:599-604, 2005
147
3251. Sarris J, Laporte E, Scholey A, et al. Does a medicinal dose of kava impair driving? A randomized, placebo-
controlled, double-blind study. Traffic Inj. Prev., 14:13-17, 2013
3252. Biswal BM, Sulaiman SA, Ismail HC, et al. Effect of Withania somnifera (ashwagandha) on the development
of chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr. Cancer Ther.,
12(4):312-322, 2013
3253. Jeyanthi T, Subramanian P. Nephroprotective effect of Withania somnifera: a dose-dependent study. Renal
Fail., 31:814-821, 2009
3254. Ali S, Banerjee S, Ahmad A, et al. Apoptosis-inducing effect of erlotinib is potentiated by 3,3'-
diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol. Cancer Ther.,
7(6):1708-1719, 2008
3255. Li X-L, Wang C-Z, Mehendale SR, et al. Panaxadiol, a purified ginseng component, enhances the anti-cancer
effects of 5-fluorouracil in human colorectal cancer cells. Cancer Chemother. Pharmacol., 64:1097-1104,
2009
3256. Wang C-Z, Xie J-T, Zhang B, et al. Chemopreventive effects of Panax notoginseng and its major constituents
on SW480 human colorectal cancer cells. Int. J. Oncol., 31:1149-1156, 2007
3257. Sikora J, Broncel M, Markowicz M, et al. Short-term supplementation with Aronia melanocarpa extract
improves platelet aggregation, clotting, and fibrinolysis in patients with metabolic syndrome. Eur. J. Nutr.,
51:549-556, 2012
3258. Luzak B, Golanski J, Rozalski, et al. Extract from Aronia melanocarpa potentiates the inhibition of platelet
aggregation in the presence of endothelial cells. Arch Med. Sci., 6(2):141-144, 2010
3259. Sayed-Ahmed MM, Nagi MN. Thymoquinone supplementation prevents the development of gentamicin-
induced acute renal toxicity in rats. Clin. Exp. Pharm. Physiol., 34:399-405, 2007
3260. Yang TH, Young YH, Liu SH. EGb 761 (Ginkgo biloba) protects cochlear hair cells against ototoxicity
induced by gentamicin via reducing reactive oxygen species and nitric oxide-related apoptosis. J. Nutrit.
Biochem., 22:886-894, 2011
3261. Smith MAL, Marely KA, Seigler D, et al. Bioactive properties of wild blueberry fruits. J. Food Sci.,
65(2):352-356, 2000
3262. Casetti F, Bartelke S, Biehler K, et al. Antimicrobial activity against bacteria with dermatological relevance
and skin tolerance of the essential oil from Coriandrum sativum L. fruits. Phytother. Res., 26:420-424,
2012
3263. Duarte A, Ferreira S, Silva F, et al. Synergistic activity of coriander oil and conventional antibiotics against
Acinetobacter baumannii. Phytomed., 19:236-238, 2012
3264. Al-Mofleh IA, Alhaider AA, Mossa JS, et al. Protection of gastric mucosal damage by Coriandrum sativum L.
pretreatment in Wistar rats. Environ. Toxicol. Pharmacol., 22:64-69, 2006
3265. Nechuta S, Shu X-O, Li H-L, et al. Prospective cohort study of tea consumption and risk of digestive system
cancers: results from the Shanghai Women's Health Study. Am J. Clin. Nur., 96:1-56-1063, 2012
3266. Bonetta A, Di Pierro F. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary
symptoms during radiotherapy for prostate carcinoma. Cancer Manag. Res., 2(4):281-286, 2012
3267. Dong H, Wang N, Zhao L, et al. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and
meta-analysis. Evid. Based Compl. Altern. Med., 2012:591654, 2012
3268. Vardy J, Dhillon HM, Clarke SJ, et al. Investigation of herb-drug interactions with Ginkgo biloba in women
receiving hormonal treatment for early breast cancer. SpringerPlus, 2:126, 2013
3269. Matthys H, Pliskevich DA, Bondarchuk OM, et al. Randomised, double-blind, placebo-controlled trial of EPs
7630 in adults with COPD. Resp. Med., 107:691-701, 2013
3270. Lucas P. Cannabis as an adjuct to or substitute for opiates in the treatment of chronic pain. J. Psychoact.
Drugs, 44(2):125-133, 2012
3271. Grotenhermen F. Pharmacokinetics and pharmcodynamics of cannabinoids. Clin. Pharmacokinet., 42(4):327-
360, 2003
3272. Os J van, Bak M, Hanssen M, et al. Cannabis use and psychosis: a longitudinal population-based study. Am. J.
Epidem., 156(4):319-327, 2002
3273. Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic ore affective mental
health outcomes: a systematic review. Lancet, 370:319-328, 2007
3274. Zammit S, Allebeck P, Andreasson S, et al. Self reported cannabis use as a risk factor for schizophrenia in
Swedish conscripts of 1969: historical cohort study. Br. Med. J., 325:1199-1202, 2002
3275. Hall W. Adverse health effects of non-medical cannabis use. Lancet, 374:1383-1391, 2009
148
3276. Li M-C, Brady JE, DiMaggio CJ, et al. Marijuana use and motor vehicle crashes. Epidemiol. Rev., 34:65-72,
2012
3277. Singla S, Sachdeva R, Mehta JL. Cannabinoids and atherosclerotic coronary heart disease. Clin. Cardiol.,
35(6):329-335, 20123278.
3278. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency. Ther. Adv. Drug Safe.,
4(3):125-133, 2013
3279. Luo FR, Paranjpe PV, Guo A, et al. Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells
overexpressing efflux transporters Pgp, CMOAT, and MRP1. Drug Metab. Dispos., 30(7):763-770, 2002
3280. Zhang W, Shi Q, Zhao L-d, et al. The safety and effectiveness of a chloroform/methanol extract of
Tripterygium wilfordii Hook F (T2) plus methotrexate in treating rheumatoid arthritis. J. Clin. Rheumatol.,
16(8):375-378, 2010
3281. Cibere J, Deng Z, Lin Y, et al. A randomized double blind, placebo controlled trial of topical Tripterygium
wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis. J. Rheumatol., 30:465-467,
2003
3282. Ji W, Li J, Lin Y, et al. Report of 12 cases of ankylosing spondylitis patients treated with Tripterygium
wilfordii. Clin. Rheumatol., 29:1067-1072, 2010
3283. Chen X, Li R, Liang T, et al. Puerarin improves metabolic functon leading to hepatoprotective effects in
chronic alcohol-induced liver injury in rats. Phytomed., 20:849-852, 2013
3284. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium sativum, Nigella sativa and
Trigonella foenum-graceum [sic] on phenytoin pharmacokinetics in beagle dogs. Phytother. Res., 2013
[doi: 10.1002/ptr.4947]
3285. Tayarani-Najaran Z, Talasaz-Firoozi E, Nasiri R, et al. Antiemetic activity of volatile oil from Mentha spicata
and Mentha x piperita in chemtherapy-induced nausea and vomiting. ecancermedicalscience, 7:290, 2013
3286. Bharani A, Ganguli A, Mathur LK, et al. Efficacy of Terminalia arjuna in chronic stable angina: a double-
blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate.
Indian Heart J., 54:170-175, 2002
3287. Vafa M, Mohammadi F, Shidfar F, et al. Effects of cinnamon consumption on glycemic status, lipid profile
and body composition in type 2 diabetic patients. Int. J. Prev. Med., 3(8):531-536, 2012
3288. Kim Y-H, Kim Y-W, Oh Y-J, et al. Protective effect of the ethanol extract of the roots of Brassica rapa on
cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats. Biol. Pharm. Bull., 29(12):2436-2441, 2006
3289. Lipska KJ, Warton EM, Huang ES, et al. HbA1c and risk of severe hypoglycemia in type 2 diabetes; the
diabetes and aging study. Diab.Care., [prepub. online; doi:10.2337/dc13-0610] July 30, 2013
3290. Virgona N, Yokotani K, Yamazaki Y, et al. Coleus forskohlii extract induces hepatic cytochrome P450
enzymes in mice. Food Chem. Tox., 50:750-755, 2012
3291. Atmaca M, Tezcan E, Kuloglu M, et al. The effect of extract Ginkgo biloba addition to olanzapine on
therapeutic effect and antioxidant enzyme levels in patients with schizophrenia. Psychiatry Clin. Neurosci.,
59:652-656, 2005
3292. Zhang W-F, Tan Y-L, Zhang Z-Y, et al. Extract of Ginkgo biloba treatment for tardive dyskinesia in
schizophrenia: a randomized, double-blind, placebo-controlled trial. J. Clin. Psychiatry, 72(5):615-621,
2011
3293. Barton DL, Liu H, Dakhil SR, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related
fatigue: a randomized, double-blind trila, NO7C2. J. Nat. Cancer Instit., [prepub. online; doi:
10.1093/jnci/djt181] July 13, 2013
3294. King ML, Adler SR, Murphy LL. Extraction-dependent effects of American ginseng (Panax quinquefolium)
on human breast cancer cell proliferation and estrogen receptor activation. Integr. Cancer Ther., 5(3):236-
243, 2006
3295. Bishop BL, Duncan MJ, Song J, et al. Cyclic AMP-regulated exocytosis of Escherichia coli from infected
bladder epithelial cells. Nat. Med., 13(5):625-630, 2007
3296. Sousa NC de, Rezende AAA de, Silva RMG da, et al. Modulatory effects of Tabebuia impetiginosa
(Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila
melanogaster. Gen. Mol. Bio., 32(2):382-388, 2009
3297. Junio HA, Sy-Cordero AA, Ettefagh KA, et al. Synergy-directed fractionation of botanical medicines: a case
study with goldenseal (Hydrastis canadensis). J. Nat. Prod., 74:1621-1629, 2011
3298. Schlesinger N, Schlesinger M. Pilot studies of cherry juice concentrate for gout flare prophylaxis. J. Arth.,
1(1):1-5, 2012
149
3299. Zhang Y, Neogi T, Chen C, et al. Cherry consumption and decreased risk of recurrent gout attacks. Arth.
Rheum., 64(12):4004-4011, 2012
3300. Haidari F Jr, Mohammad Shahi M, Keshavarz SA, et al. Inhibitory effects of tart cherry (Prunus cerasus)
juice on xanthine oxidoreductase activity and its hypouricemic and antioxidant effects on rats. Malays. J.
Nutr., 15(1):53-64, 2009
3301. Seeram NP, Momin RA, Nair MG, et al. Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in
cherries and berries. Phytomed., 8(5):362-369, 2001
3302. Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare
prophylaxis: comment on the article by Zhang et al. Arth. Rheum., 65(4):1135-1136, 2013
3303. Doroshyenko O, Rokitta D, Zadoyan G, et al. Drug cocktail interaction study on the effect of the orally
administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers. Drug
Metab. Dispos., 41:987-993, 2013
3304. Teschke R, Glass X, Schulze J. Herbal hepatotoxicity by greater celandine (Chelidonium majus): causality
assessment of 22 spontaneous reports. Reg. Toxicol. Pharmacol., 61:282-291, 2011
3305. Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a
randomized, placebo-controlled trial. Can. Med. Assoc. J., 184(10):1143-1150, 2012
3306. Shokeen P, Bala M, SIngh M, et al. Invitro activity of eugenol, an active component from Ocimum sanctum,
against multiresistant and susceptible strains of Neisseria gonorrhaeae. Int. J. Antimicrob. Agents, 32:174-
179, 2008
3307. Shokeen P, Ray K, Bala M, et al. Preliminary studies on activity of Ocimum sanctum, Drynaria quecifolia,
and Annona squamosa against Neisseria gonorrhoeae. Sex. Trans. Dis., 32(2):106-111, 2005
3308. Rai V, Mani UV, Iyer UM. Effect of Ocimum sanctum leaf powder on blood lipoproteins, glycated proteins
and total amino acids in patients with non-insulin-dependent diabetes mellitus. J. Nutr. Envir. Med., 7:113-
118, 1997
3309. Kochhar A, Sharma N, Sachdeva R. Effect of supplementation of tulsi (Ocimum sanctum) and neem
(Azadirachta indica) leaf powder on diabetic symptoms, anthropometric parameters and blood pressure of
noninsulin dependent male diabetics. Ethno-Med., 3(1):5-9, 2009
3310. Hannan JMA, Marenah L, Ali L, et al. Ocimum sanctum leaf extracts stimulate insulin secretion from
perfused pancreas, isolated islets and clonal pancreatic -cells. J. Endocrin., 189:127-136, 2006
3311. Bhat M, Zinjarde SS, Bhargava SY, et al. Antidiabetic Indian plants: a good source of potent amylase
inhibitors. Evid. Based Compl. Altern. Med., #810207 [doi:10.1093/ecam/nen040], 2011
3312. Salem EM, Yar T, Bamosa AO, et al. Comparative study of Nigella sativa and triple therapy in eradication of
Helicobacter pylori in patients with non-ulcer dyspepsia. Saudi J. Gastroent., 16(3):207-214, 2010
3313. Chitra V, Devi KB, Lokesh AG, et al. Pharmacodynamic interaction of aqueous extract of garlic with
atorvastatin in doxorubicin-induced cardiotoxicity in rats. Int. J. Pharm. Pharmaceut. Sci., 5(Suppl. 2):440-
449, 2013
3314. Haghighi M, Khalvat A, Toliat T, et al. Comparing the effects of ginger (Zingiber officinale) extract and
ibuprofen on patients with osteoarthritis. Arch. Iran. Med., 8(4):267-271, 2005
3315. Drozdov VN, Kim VA, Tkachenko EV, et al. Influence of a specific ginger combination on gastropathy
conditions in patients with osteoarthrits of the knee or hip. J. Altern. Compl. Med., 18(6):583-588, 2012
3316. Wigler I, Grotto I, Caspi D, et al. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis.
Osteoarth. Cart., 11:783-789, 2003
3317. Mannucci C, Navarra M, Calzavara E, et al. Serotonin involvement in Rhodiola rosea attenuation of nicotine
withdrawal signs in rats. Phytomed., 19:1117-1124, 2012
3318. Nada AS, Hawas AM, Amin NED, et al. Radioprotective effect of Curcuma longa extract on -irradiation-
induced oxidative stress in rats. Can. J. Physio. Pharmacol., 90:415-423, 2012
3319. Yin H, Guo R, Xu Y, et al. Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer.
Acta Biochim. Biophys. Sin., 44:147-153, 2012
3320. Zi X, Mukhtar H, Agarwal R. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin:
inhibition of mRNA expression of an endogenous tumor promoter TNF. Biochem. Biophys. Res. Comm.,
239:334-339, 1997
3321. Sepahvand R, Esmaeili-Mahani S, Arzi A, et al. Ginger (Zingiber officinale Roscoe) elicits antinociceptive
properties and potentiates morphine-induced analgesia in the rat radiant heat tail-flick test. J. Med. Food,
13(6):1397-1401, 2010
150
3322. Na DH, Ji HY, Park EJ, et al. Evaluation of metabolism-mediated herb-drug interactions. Arch. Pharm. Res.,
34(11):1829-1842, 2011
3323. Zhang JS, Sigdestad CP, Gemmell MA, et al. Modification of radiation response in mice by fractionated
extracts of Panax ginseng. Rad. Res., 112:156-163, 1987
3324. Song JY, Han SK, Bae KG, et al. Radioprotective effects of ginsan, an immunomodulator. Rad. Res.,
159:768-774, 2003
3325. Yun TK, Choi SY. Preventive effect of ginseng intake against various human cancers: a case-control study on
1987 pairs. Cancer Epidem. Biomark. Prev., 4:401-408, 1995
3326. Cypulska P, Thakur SD, Foster BC, et al. Extracts of Canadian First Nations medicinal plants, used as natural
products, inhibit Neisseria gonorrhoeae isolates with different antibiotic resitance profiles. Sex. Trans.
Dis., 38(7):667-671, 2011
3327. Chovanova R, Mikulasova M, Vaverkova S. In vitro antibacterial and antibiotic resistance modifying effect of
bioactive plant extracts on methicillin-resistant Staphylococcus epidermidis. Int. J. Microbiol.,
2013:#760969(6 pp.), 2013
3328. Lowcock EC, Cotterchio M, Boucher BA. Consumption of flaxseed, a rich source of lignans, is associated
with reduced breast cancer. Cancer Causes Control, 24:813-816, 2013
3329. Jacob RA, Sapinozzi GM, Simon VA, et al. Consumption of cherries lowers plasma urate in healthy women.
J. Nutr., 133:1826-1829, 2003
3330. Sheng Y, Bryngelsson C, Pero RW. Enhanced DNA repair, immune function and reduced toxicity of C-MED-
100™, a novel aqueous extract from Uncaria tomentosa. J. Ethnopharm., 69:115-126, 2000
3331. Sheng Y, Pero RW, Wagner H. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous
extract from Uncaria tomentosa. Phytomed., 7(2):137-143, 2000
3332. Choi JS, Han JY, Ahn HK, et al. Fetal and neonatal outcomes in women reporting ingestion of licorice
(Glycyrrhiza uralensis) during pregnancy. Planta Med., 79:97-101, 2013
3333. Khurana H, Pandey RK, Saksena AK, et al. An evaluation of vitamin E and pycnogenol in children suffering
from oral mucositis during cancer chemotherapy. Oral Dis., 19:456-464, 2013
3334. Huang L, Bi HC, Liu Yh, et al. CAR-mediated up-regulation of CYP3A4 expression in LS174T cells by
Chinese herbal compounds. Drug Metab. Pharmacokinet., 26(4):331-340, 2011
3335. Chi YC, Juang SH, Chui WK, et al. Acute and chronic administrations of Rheum palmatum reduced the
bioavailability of phenytoin in rats: a new herb-drug interaction. Evid. Based Compl. Altern. Med.,
2012:#701205(9 pp.)[doi:10.1155/2012/701205], 2012
3336. Lee YS, Kand OH, Choi JG, et al. Synergistic effect of emodin in combination with ampicillin or oxacillin
against methicillin-resistant Staphylococcus aureus. Pharm. Biol., 48(11):1285-1290, 2010
3337. Joung DK, Joung H, Yang DW, et al. Synergistic effect of rhein in combination with ampicillin or oxacillin
against methicillin-resistant Staphylococcus aureus. Exp. Ther. Med., 3:608-612, 2012
3338. Wang CZ, Basila D, Aung HH, et al. Wang CZ, Basila D, Aung HH, et al. Effects of Ganoderma lucidum
extract on chemotherapy-induced nausea and vomiting in a rat model. Am. J. Chin. Med., 33(5):807-815,
2005
3339. Chen T, Yan F, Qian, et al. Randomized phase II trial of lyophilized strawberries in patients with dysplastic
precancerus lesions of the esophagus. Cancer Prev. Res., 5(1):41-50, 2011
3340. Kodama N, Yamada M, Nanba H. Addition of maitake D-fraction reduces the effective dosage of vancomycin
for the treatment of Listeria-infected mice. Jpn. J. Pharmacol., 87:327-332, 2001
3341. Kodama N, Komuta K, Nanba H. Can maitake MD-franction aid cancer patients? Altern. Med. Rev., 7(3):236-
239, 2002
3342. Asdaq SM, Inamdar MN. Potential of garlic and its active constituent, S-allyl cysteine, as antihypertensive
and cardioprotective in presence of captopril. Phytomed., 17:1016-1026, 2010
3343. Tadic VM, Dobric S, Markovic GM, et al. Anti-inflammatory, gastroprotective, free-radical-scavenging, and
antimicrobial activities of hawthorn berries ethanol extract. J. Agric. Food Chem., 56:7700-7709, 2008
3344. Jalali AS, Hasanzadeh S, Malekinejad H. Crataegus monogyna aqueous extract ameliorates
cyclophosphamide-induced toxicity in rat testis: stereological evidences. Acta med. Iran., 50(1):1-8, 2012
3345. Ustyuzhanina NE, Ushakova NA, Zyuzina KA, et al. Influence of fucoidans on hemostatic system. Mar.
Drugs, 11:2444-2458, 2013
151
3346. Leitzman P, Narayanapillai SC, Balbo S, et al. Kava blocks 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-
induced lung tumorigenesis in association with reducing O 6-methylguanine DNA adduct in A/J mice.
Cancer Prev. Res., 7(1):86-96, 2014
3347. Prakash UNS, Srinivasan K. Gastrointestinal protective effect of dietary spices during ethanol-induced
oxidant stress in experimental rats. Appl. Physiol. Nutr. Metab., 35:134-141, 2010
3348. Sanmukhani J, Satodia V, Trivedi J, et al. Efficacy and safety of curcumin in major depressive disorder: a
randomized controlled trial. Phytother. Res., [prepub. online doi:10.1002/ptr.5025], 2013
3349. Ushimaru PI, Barbosa LN, Fernandes AAH, et al. In vitro antibacterial activity of medicinal plant against
Escherichia coli strains from human clinical specimens and interactions with antimicrobial drugs. Nat
Prod. Res., 26(16):1553-1557, 2012
3350. Quave CL, Plano LRW, Pantuso T, et al. Effects of extracts from Italian medicinal plants on planktonic
growth, biofilm formation and adherence of methicillin-resistant Staphylococcus aureua. J.
Ethnopharmacol., 118(3):418-428, 2008
3351. Udani JK. Immunomodulatory effects of ResistAid™: a randomized, double-blind, placebo-controlled,
multidose study. J. Am. Coll. Nutr., 32(5):331-338, 2013
3352. Ahangarpour A, Mohammadian M, Dianat M. Antidiabetic effect of hydroalcoholic Urtica dioica leaf extract
in male rats with fructose-induced insulin resistance. Iran. J. Med. Sci., 37(3):181-186, 2012
3353. Amin A. Ketoconazole-induced testicular damage in rats reduced by Gentiana extract. Exp. Toxic. Path.,
59:377-384, 2008
3354. Rho JK, Choi YJ, Jeon BS, et al. Combined treatment with silibinin and epidermal growth factor receptor
tyosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Mol. Cancer Ther.,
9(12):3233-3243, 2010
3355. Cufi S, Bonavia R, Vazquez-Martin A, et al. Silibinin suppresses EMT-driven erlotinib resistance by
reversing the high miR-21/low miR-200c signature in vivo. Sci. Rep., 3:2459[doi:10.1038/srep02459] (10
pp.), 2013
3356. Zhang X, Zhang H, Tighiouart M, et al. Synergistic inhibition of head and neck tumor growth by green tea
(−)-epigallocatechin-3-gallate and EGFR tyosine kinase inhibitor. Int. J. Cancer, 123:1005-1014, 2008
3357. Amin ARMR, Khuri FR, Chen ZG, et al. Synergistic growth inhibition of squamous cell carcinoma of the
head and neck by erlotinib and epigallocatechin-3-gallate: the role of p53-dependent inhibition of nuclear
factor-B. Cancer Prev. Res., 2(6):538-545, 2009
3358. Milligan SA, Burke P, COleman DT, et al. The green tea polyphenol EGCG potentiates the antiproliferative
activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells. Clin.
Cancer Res., 15(15):4885-4894, 2009
3359. Hejazi J, Rastmanesh R, Taleban FA, et al. A pilot clinical trial of radioprotective effects of curcumin
supplementation in patients with prostate cancer. J. Cancer Sci. Ther.,5(10):320-324, 2013
3360. Butler LM, Wu AH. Green and black tea in relation to gynecologic cancers. Mol. Nutr. Food Res., 55:931-
940, 2011
3361. Rhodes LE, Darby G, Massey KA, et al. Oral green tea catechin metabolites are incorporated into human skin
and protect against UV radiation-induced cutaneous inflammation in association with reduced production
of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid. Br. J. Nutr., 110:891-900, 2013
3362. Clayton NP, Yoshizawa K, Kissling GE, et al. Immunohistochemical analysis of expressions of hepatic
cytochrome P450 in F344 rats following oral treatment with kava extract. Exp. Toxicol. Pathol., 58(4):223-
236, 2007
3363. Belcaro G, Hosoi M, Pellegrini L, et al. A controlled study of a lecithinized delivery system of curcumin
(Meriva®) to alleviate the adverse effects of cancer treatment. Phytother. Res., 28:444-450, 2014
3364. Gamboa-Gomez C, Salgado LM, Gonzalez-Gallardo A, et al. Consumption of Ocimum sanctum L. and Citrus
paradisi infusions modulates lipid metabolism and insulin resistance in obese rats. Food Func., 5:927-935,
2014
3365. Sun Y, Tang J, Gu X, et al. Water-soluble polysaccharides from Angelica sinensis (Oliv.) Diels: preparation,
characterization and bioactivity. Int. J. Biol Macromol.,36:283-289, 2005
3366. Zhang S, Qin C, Safe SH. Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure
and cell context. Env. Health Perspec., 111(16):1877-1882, 2003
3367. Cho CH, Bae JS, Kim YU. 5-reductase inhibitory components as antiandrogens from herbal medicine. J.
Acupunct. Meridian Stud., 3(2):116-118, 2010
3368. Nabekura T, Yamaki T, Ueno K, et al. Inhibition of P-glycoprotein and multidrug resistance protein 1 by
dietary phytochemicals. Cancer Chemother. Pharmacol., 62:867-873, 2008
152
3369. Strippoli S, Lorusso V, Albano A, et al. Herbal-drug interaction induced rhabdomyolysis in a liposarcoma
patient receving trabectedin. BMC Compl. Altern. Med., 13:199(5 pp.), 2013
3370. Zuo GY, Meng FY, Hao XY, et al. Antibacterial alkaloids from Chelidonium majus Linn (Papaveeraceae)
against clinical isolates of methicillin-resistant Staphylococcus aureus. J. Pharm. Pharmaceut. Sci.,
11(4):90-94, 2008
3371. Sakr FM, Gado AM, Mohammed HR, et al. Preparation and evaluation of a multimodal minoxidil
microemulsion versus minoxidil alone in the treatment of androgenic alopecia of mixed etiology: a pilot
study. Drug Des. Dev. Ther., 7:413-423, 2013
3372. Abad ANA, Nouri MHK, Tavakkoli F. Effect of Salvia officinalis hydroalcoholic extract on vincristine-
induced neuropathy in mice. Chin. J. Nat. Med., 9(5):354-358, 2011
3373. Ozturk G, Anlar O, Erdogan E, et al. The effect of ginkgo extract EGb761 in cisplatin-induced peripheral
neuropathy in mice. Toxicol. Appl. Pharmacol., 196:169-175, 2004
3374. Abad ANA, Nouri MHK, Gharjanie A, et al. Effect of Matricaria chamomilla hydroalcoholic extract on
cisplatin-induced neuropathy in mice. Chin. J. Nat. Med., 9(2):126-131, 2011
3375. Muthuraman A, Singh N. Attenuating effect of hydroalcoholic extract of Acorus calamus in vincristine-
induced painful neuropathy in rats. J. Nat. Med., 65:480-487, 2011
3376. Gupta VK, Verma S, Gupta S, et al. Membrane-damaging potential of natural L-(-)-usnic acid in
Staphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis., 31:3375-3383, 2012
3377. Adams JD Jr, Garcia C. Women's health among the Chumash. eCAM, 3(1):125-131, 2006
3378. Barnes J, Barber N, Wheatley D, et al. A pilot randomised, open, uncontrolled, clinical study of two dosages
of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural
support in smoking cessation. Planta Med., 72:378-382, 2006
3379. Parsons A, Ingram J, Inglis J, et al. A proof of concept randomised placebo controlled factorial trial to
examine the efficacy of St Joh's wort for smoking cessation and chromium to prevent weight gain on
smoking cessaton. Drug Alc. Depend., 102:116-122, 2009
3380. Zhang M Li L, Liu P, et al. Green tea for the prevention of cancer: evidence of field epidemiology. Funct.
Foods Health Dis., 2(10)339-350, 2012
3381. Wang Y, Zhang S, Iqbal S, et al. Pomegranate extract inhibits the bone metastatic growth of human prostate
cancer cells and enhances the in vivo efficacy of docetaxel chemotherapy. Prostate, 74:497-508, 2014
3382. Raji Y, Oloyede GK. Antiulcerogenic effects and possible mechanism of action of Quassia amara (L.
Simaroubaceae) extract and its bioactive principles in rats. Afr. J. Tradit. Complement. Altern. med.,
9(1):112-119, 2012
3383. Garcia-Barrantes PM, Badilla B. Anti-ulcerogenic properties of Quassia amara L. (Simaroubaceae)
standardized extracts in rodent models. J. Ethnopharmacol., 134:904-910, 2011
3384. Toma W, Gracioso JS, Andrade FDP, et al. Antiulcerogenic activity of four extracts obtained from the bark
wood of Quassia armara L. (Simaroubaceae). Biol. Pharm. Bull., 25(9):1151-1155, 2002
3385. Tan KW, Cooney J, Jensen D, et al. Hop-derived prenylflavonids are substrates and inhibitors of the efflux
transporter breast cancer resistance protein (PCRP/ABCG2). Mol. Nut. Food Res., 12 pp.[online prepub.:
doi.10.1002/mnfr.201400288], 2014
3386. Anoush M, Eghbal MA, Fathiazad F, et al. The protective effects of garlic extract against acetaminophen-
induced oxidative stress and glutathione depletion. Pak. J. Biol. Sci., 12(10):765-771, 2009
3387. Ademiluyi AO, Oboh G, Owoloye TR, et al. Modulatory effects of dietary inclusion of garlic (Allium sativum)
on gentamycin-induced heptotoxicity and oxidative stress in rats. Asian Pac. J. Trop. Biomed., 3(6):470-
475, 2013
3388. Misaka S, Yatabe J, Muller F, et al. Green tea ingestion greatly reduces plasma concentrations of nadolol in
healthy subjects. Clin. Pharm. Ther., 95(4):432-438, 2014
3389. Ahmed KM. The effect of olive leaf extract in decreasing the expression of two pro-inflammatory cytokines in
patients receiving chemotherapy for cancer. A randomized clinical trial. Saudi Dent. J., 25:141-147, 2013
3390. Miyanaga N, Akaza H, Hinotsu S, et al. Prostate cancer chemoprevention study: an investigative randomized
control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci.,
103(1):125-130, 2012
3391. Nneli RO, Woyike OA. Antiulcerogenic effects of coconut (Cocos nucifera) extract in rats. Phytother. Res.,
22:970-972, 2008
3392. Wiegman DJ, Brinkman K, Franssen EJR. Interaction of Ginkgo biloba with efavirenz. AIDS, 23(9):1184-
1185, 2009
153
3393. Balunas MJ, Kinghorn AD. Natural compounds with aromatase inhibitory activity: an update. Planta Med.,
76:1087-1093, 2010
3394. Nathan J, Panjwani S, Mohan V, et al. Efficacy and safety of standardized extract of Trigonella foenum-
graecum L seeds as an adjuvant to L-dopa in the management of patients with Parkinson's disease.
Phytother. Res., 28:172-178, 2014
3395. Tiwari V, Chopra K. Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents
cognitive deficits in rats postnatally exposed to ethanol. Psychopharm., 224:519-535, 2012
3396. Rinwa P, Kumar A. Piperine potentiates the protective effects of curcumin against chronic unpredictable
stress-induced cognitive impairment and oxidative damage in mice. Brain Res., 1488:38-50, 2012
3397. Wise LE, Premearatne ID, Gamage TF, et al. L-theanine attenuates abstinence signs in morphine-dependent
rhesus monkeys and elicits anxiolytic-like activity in mice. Pharmacol. biochem. Behav., 103(2):245-252,
2012
3398. Zou DM, Brewer M, Garcia F, et al. Cactus pear: a natural product in cancer chemoprevention. Nutrit. J.,
4:25(12 pp.), 2005
3399. Hudson EA, Howells LM, Gallacher-Horley B, et al. Growth-inhibitory effects of the chemopreventive agent
indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour
cell line. BMC Cancer, 3:2, 2003
3400. Cornblatt BS, Ye L, Dinkova-Kostova AT, et al. Preclinical and clinical evaluation of sulforaphane for
chemoprevention in the breast. Carcinogen., 28(7):1485-1490, 2007
3401. Munday R, Mhawech-Fauceglia P, Munday CM, et al. Inhibition of urinary bladder carcinogenesis by
broccoli sprouts. Cancer Res., 68(5):1593-1600, 2008
3402. Li Y, Zhang T, Korkaya H, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits
breast cancer stem cells. Clin. Cancer Res., 16(9):2580-2590, 2010
3403. Guerrero-Beltran CE, Mukhopadhyay P, Horvath B, et al. Bulforaphane, a natural constituent of broccoli,
prevents cell death and inflammation in nephropathy. J. Nutr. Biochem., 23(5):494-500, 2012
3404. Bachhuber MA, Saloner B, Cunningham CO, et al. Medical cannabis laws and opioid analgesic overdose
mortality in the United States, 1999-2010. JAMA Intern. Med., [online prepub.
doi:10.1001/jamainternmed.2014.4005], Aug. 25, 2014
3405. West R, Zatonski W, Cedzynska M, et al. Placebo-controlled trial of cytisine for smoking cessation. New
Engl. J. Med., 365(13):1193-1200, 2011
3406. Zijp IM, Korver O, Tijburg LBM. Effect of tea and other dietary factors on iron absorption. Crit. Rev. Food
Sci. Nutr., 40(5):371-398, 2000
3407. Panahi Y, Saadat A, Beiraghdar F, et al. Adjuvant therapy with bioavailability-boosted curcuminoids
suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized
double-blind placebo-controlled trial. Phytother. Res., 28(10):1461-1467, 2014
3408. Reshma K, Rao AV, Dinesh M, et al. Effect of Ocimum flavonoids as a radioprotector on the erythrocyte
antioxidants in oral cancer. Ind. J. Clin. Biochem., 20(1):160-164, 2005
3409. Thani NAA, Keshavarz S, Lwaleed BA, et al. Cytotoxicity of gemcitabine enhance by polyphenolics from
Aronia meanocarpa in pancreatic cancer cell line AsPC-1. J. Clin. Pathol., 67(11):949-954, 2014
3410. Brahmi D, Ayed Y, Hfaiedh M, et al. Protective effect of cactus cladode extract against cisplatin induced
oxidative stress, genototxicity and apoptosis in balb/c mice: combination with phytochemical composition.
BMC Compl. Altern. Med., 12:111(14pp.), 2012
3411. Morgia G, Russo GI, Voce S, et al. Serenoa repens, lycopene and selenium versus tamsulosin for the
treatment of LUTS/BPH. An Italian multicenter double-blind randomized study between single or
combination therapy (PROCOMB trial). Prostate, 74(15):1471-1480, 2014
3412. Mucalo I, Jovanovski E, Vuksan V, et al. American ginseng extract (Panax quinquefolius L.) is safe in long-
term use in type 2 diabetic patients. Evid. Base Compl. Altern. Med., 2014:#969168(6 pp.), 2014
3413. Azadmehr A, Ziaee A, Ghanei L, et al. A randomized clinical trial study: anti-oxidant, anti-hyperglycemic and
anti-hyperlipidemic effects of olibanum gum in type 2 diabetic patients. Iran. J. Pharm. Res., 13(3):1003-
1009, 2014
3414. Busetto GM, Giovannone R, Ferro M, et al. Chronic bacterial prostatitis: efficacy of short-lasting antibiotic
therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens
[sic] and arbutin (Lactorepens®). BMC Urol., 14:53(9 pp.), 2014
3415. Appleboom T, Maes N, Albert A. A new Curcuma extract (Flexofytol®) in osteoarthrits: results from a
Belgian real-life experience. Open Rheum. J., 8:77-81, 2014
154
3416. Younesy S, Amiraliakbari S, Esmaeili S, et al. Effects of fenugreek seed on the severity and systemic
symptoms of dysmenorrhea. J. Reprod. Infertil., 15(1):41-48, 2014
3417. Montazeri AS, Hamidzadeh A, Raei M, et al. Evaluation of oral ginger efficacy against postoperative nausea
and vomiting: a randomized double-blinded clinical trial. Iran. Red Crescent Med. J., 15(12):e12268(6
pp.), 2013
3418. Ahang JH, Wang JP, Wang HJ. Clinical study on effect of total Panax notoginseng saponins on immune
related inner environment imbalance in rheumatoid arthritis patients. [English abstract of Chinese article]
Zhongguo Zhong Xi Yi Jie He Za Zhi, 27(7):589-592, 2007
3419. Argirovic A, Argirovic D. Does the addition of Serenoa repens to tamsulosin improve its therapeutical
efficacy in benign prostatic hyperplasia? Vojnosanit. Pregl., 70(12):1091-1096, 2013
3420. Mucalo I, Jovanovski E, Rahelic D, et al. Effect of American ginseng (Panax quinquefolius L.) on arterial
stiffness in subjects with type-2 diabetes and concomitant hypertension. J. Ethnopharm., 150:148-153,
2013
3421. Gibbons S, Leimkugel J, Oluwatuyi M, et al. Activity of Zanthoxylum clava-herculis extracts against multi-
drug resistant methicillin-resistant Staphylococcus aureus (mdr-MRSA). Phytother. Res., 17:274-275, 2003
3422. Sadowska B, Paszkiewicz M, Podsedek A, et al. Vaccinium myrtillus leaves and Frangula alnus bark derived
extracts as potential antistaphylococcal agents. Acta Biochim. Polon., 61(1):163-169, 2014
3423. Rodrigues M, Alves G, Lourenco N, et al. Herb-drug interaction of Paullinia cupana (guarana) seed extract
on the phamracokinetics of amiodarone in rats. Evid. Based Compl. Altern. Med., 2012:#428560(10 pp.),
2012
3424. Qiu F, Zeng J, Liu S, et al. Effects of danshen ethanol extract on the pharmacokinetics of fexofenadine in
healthy volunteers. Evid. Based Compl. Altern. Med., 2014:#473213(5 pp.), 2014
3425. Qiu F, Jiang J, Ma Y, et al. Opposite effects of single-dose and multidose administration of the ethanol extract
of danshen on CYP3A in healthy volunteers. Evid. Based Compl. Altern. Med., 2013:#730734(8 pp.), 2013
3426. Xiao Y-J, Hu M, Tomlinson B. Effects of grapefruit juice on cortisol metabolism in healthy male Chinese
subjects. Food Chem. Toxicol., 74:85-90, 2014
3427. Saruwatari A, Isshiki M, Tamura H. Inhibitory effects of various beverages on the sulfoconjugation of 17-
estradiol in human colon carcinoma Caco-2 cells. Biol. Pharm. Bull., 31(11):2131-2136, 2008
3428. Kedzierska M, Malinoswska J, Kontek B, et al. Chemotherapy modulates the biological activity of breast
cancer patients plasma: the protective properties of black chokeberry extract. Food Chem. Toxicol., 53:126-
132, 2013
3429. Szaefer H, Krajka-Kuzniak V, Ignatowicz E, et al. Chokeberry (Aronia melanocarpa) juice modulates 7,12-
dimethylbenz[a]anthracene induced hepatic but not mammary gland phase I and II enzymes in female rats.
Environ. Toxicol. Pharmacol., 31:339-346, 2011
3430. Franco P, Potenza I, Moretto F, et al. Hypericum perforatum and neem oil for the management of acute skin
toxicity in had and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective
observational study. Radiat. Onco., 9:1164(13 pp.), 2014
3431. Hamilton K, Bennett NC, Purdie G, et al. Standardized cranberry capsules for radiation cystitis in prostate
cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study. Support.
Care Cancer, 23:95-102, 2015
3432. Guo L-d, Shen Y-q, ZhaoX-h, et al. Curcumin combined with oxaliplatin effectively suppress colorectal
carcinoma in vivo through inducing apoptosis. Phytother. Res., 29:357-365, 2015
3433. Panahi Y, Rahimnia A-R, Sharafi M, et al. Curcuminoid treatement for knee osteoarthritis: a randomized
double-blind placebo-controlled trial. Phytother. Res., 28:1625-1631, 2014
3434. Hizli F, Uygur MC. A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens
plus tamsulosin treatment for patients with benign prostate hyperplasia. Int. Urol. Nephrol., 39:879-886,
2007
3435. Baugher BW, Berman M, Dierksen JE, et al. Digoxin immunoassays on the ARCHITECT i2000SR and
ARCHITECT c8000 analyzers are free from interfenences of Asian, SIberian, and American ginseng. J.
Clin. Lab. Anal., 29:1-4, 2015
3436. Valcheve-Kuzmanova S, Stavreva G, Dancheva V, et al. Effect of Aronia melanocarpa fruit juice on
amiodarone-induced pneumotoxicity in rats. Pharmacogn. Mag., 10(38):132-140, 2014
3437. Bonyadi MHJ, Yazdani S, Saadat S. The ocular hypotensive effect of saffron extract in primary open angle
glaucoma: a pilot study. BMC Compl. Altern. Med., 14:#399(6 pp.), 2014
155
3438. Stage TB, Pedersen RS, Damkier P, et al. Intake of St. John's wort improves the glucose tolerance in healthy
subjects who ingest metformin compared with metformin alone. Br. J. Clin. Pharmacol., 79(2):298-306,
2015
3439. Miller DK, Crooks PA, Teng L, et al. Lobeline inhibits the neurochemical and behavioral effects of
amphetamine. J. Pharmacol. Exper. Ther., 296(3):1023-1034, 2001
3440. Harrod SB, Dwoskin LP, Crooks PA, et al. Lobeline attenuates d-methamphetamine self-administration in
rats. J. Pharmacol. Exper. Ther., 298(1):172-179, 2001
3441. Tatsuta T, Kitanaka N, Kitanaka J, et al. Lobeline attenuates methamphetamine-induced stereotypy in
adolescent mice. Neurochem. Res., 31:1359-1369, 2006
3442. Ma Y, Wink M. Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance
in tumor cells. Phytomed., 15:754-758, 2008
3443. Qiu F, Wang G, Zhang R, et al. Effect of danshen extract on the activity of CYP3A4 in healthy volunteers. Br.
J. Clin. Pharmacol., 69(6):656-662, 2010
3444. Wu WWP, Yeung JHK. Inhibition of warfarin hydroxylation by major tanshinones of danshen (Salvia
miltiorrhiza) in the rat in vitro and in vivo. Phytomed., 17:219-226, 2010
3445. Kohler S, Funk P, Kiesser M. Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on
bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers.
Bl. Coagul. Fibrinolysis, 15:303-309, 2004
3446. Liu JF, Srivatsa A, Kaul V. Black licorice ingestion: yet another confounding agent in patients with melena.
World J. Gastroint. Surg., 2(1):30-31, 2010
3447. Mauricio I, Francischetti B, Monteiro RQ, et al. Identification of glycyrrhizin as a thrombin inhibitor.
Biochem. Biophys. Res. Comm., 235:259-263, 1997
3448. Rivera CA, Ferro CL, Bursua AJ, et al. Probable interaction between Lycium barbarum (goji) and warfarin.
Pharmacother., 32(3):e50-e53, 2012
3449. Verma SK, Bordia A. Ginger, fat and fibrinolysis. Ind. J. Med. Sci., 55(2):83-86, 2001
3450. Lau A-J, Toh D-F, Chua T-K, et al. Antiplatelet and anticoagulant effects of Panax notoginseng: comparison
of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium. J. Ethnopharm.,
125:380-386, 2009
3451. Wang J, Huang Z, Cao H, et al. Screening of anti-platelet aggregation agents from Panax notoginseng using
human platelet extraction and HPLC−DAD−ESI-MS/MS. J. Sep. Sci., 31:1173-1180, 2008
3452. Park SH, Oh MR, Choi EK, et al. An 8-wk, randomized, double-blind, placebo-controlled clinical trail for the
antidiabetic effects of hydrolyzed ginseng extract. J. Ginseng Res., 38:239-243, 2014
3453. Schneider FH, Mione PJ, Raheman FS, et al. Reduction of tobacco withdrawal symptoms by sublingual
lobeline sulfate. Am. J. Health Behav., 20(5):346-363, 1996
3454. Glover ED, Leischow SJ, Rennard SI, et al. A smoking cessation trial with lobeline sulfate: a pilot study. Am.
J. Health Behav., 22(1):62-74, 1998
3455. Maser E, Friebertshauser J, Volker B. Purification, characterization and NNK carbonl reductase activities of
11b-hydroxysteroid dehydrogenase type 1 from human liver: enzyme cooperativity and significant in the
detoxification of a tobacco-derived carcinogen. Chem. Biol. Interact., 143-144:435-448, 2003
3456. Jaliki C, Salahshoor MR, Naseri A. Protective effect of Urtica dioica L against nicotine-induced damage on
sperm parameters, testosterone and testis tissue in mice. Iran.j. Reprod. Med., 12(6):401-408, 2014
3457. Dietz BM, Hagos GK, Eskra JN, et al. Differential regulation of detoxification enzymes in hepatic and
mammary tissue by hops (Humulus lupulus) in vitro and in vivo. Mol. Nutr. Food Res., 57(6): 2013
3458. Chen S, Oh SR, Phung S, et al. Anti-aromatase activity of phytochemicals in white button mushrooms
(Agaricus bisporus). Cancer Res., 66(24):12026-12034, 2006
3459. Di X, Wang X, Di X, et al. Effect of piperine on the bioavailability of pharmacokinetics of emodin in rats. J.
Pharmaceut. Biomed. Anal., 115:144-149, 2015
3460. Micota B, Saowska B, Podsedek A, et al. Leonurus cardiaca L. herb − a derived extract and an ursolic acid as
the factors affecting the adhesion capacity of Staphylococcus aureus in the context of infective
endocarditis. Acta Biochim. Polon., 61(2):385-388, 2014
3461. Ebrahimie M, Bahmani M, Shirzad H, et al. A review study of the effect of Iranian herbal medicines on opioid
withdrawal syndrome. J. Evid. Based Compl. Altern. Med., [online prepub. doi:
10.1177/2156587215577896] 8 pp., Mar. 26, 2015
3462. Feily A, Abbasi N. The inhibitory effect of Hypericum perforatum extract on morphine withdrawal syndrome
in rat and comparison with clonidine. Phytother. Res., 23:1549-1552, 2009
156
3463. Grover JK, Rathi SS, Vats V. Preliminary study of fresh juice of Benincasa hispida on morphine addiction in
mice. Fitoterapia, 71:707-709, 2000
3464. Hosseinzadeh H, Nourbakhsh M. Effect of Rosmarinus officinalis L. aerial parts extract on morphine
withdrawal syndrome in mice. Phytother. Res., 17:938-941, 2003
3465. Hosseinzadeh H, Jahanian Z. Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and
safranal, on morphine withdrawal syndrome in mice. Phytother. Res., 24:726-730, 2010
3466. Kasture S, Vinci S, Ibba F, et al. Withania somnifera prevents morphine withdrawal-induced decrease in spine
density in nucleus accumbens shell of rats: a confocal laser scanning microscopy study. Neurotox. Res.,
16:343-355, 2009
3467. Scandlyn MJ, Stuart EC, Somers-Edgar TJ, et al. A new role for tamoxifen in oestrogen receptor-negative
breast cancer when it is combined with epigallocatechin gallate. Br. J. Cancer, 99:1056-1063, 2008
3468. Huang H-C, Way T-D, Lin C-L, et al. EGCG stabilies p27kip1 in E2-stimulated MCF-7 cells through down-
regulation of the Skp2 protein. Endocrin., 149(2):5972-5983, 2008
3469. Chisholm K, Bray BJ, Rosengren RJ. Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to
MDA-MB-231 human breast cancer cells. Anti-Cancer Drugs, 15:889-897, 2004
3470. Stuart EC, Rosengren RJ. The combination of raloxifene and epigallocatechin gallate suppresses growth and
induces apoptosis in MDA-MB-231 cells. Life Sci., 82:943-948, 2008
3471. Prakash UNS, Srinivasan K. Enhanced intestinal uptake of iron, zinc and calcium in rats fed pungent spice
principles - piperine, capsaicin and ginger (Zingiber officinale). J. Trace Elem. Med. Biol., 27:184-190,
2013
3472. Chiang H-M, Chao P-DL, Wen K-C, et al. Ginger significantly decreased the oral bioavailability of
cyclosporine in rats. Am J. Chin. Med., 34(5):845-855, 2006
3473. Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents acetaminophen-induced acute
hepatotoxicity by enhancing hepatic antioxidant status. Food Chem. Toxicol., 45:2267-2272, 2007
3474. Yemitan OK, Izegbu MC. Protective effects of Zingiber officinale (Zingiberaceae) against carbon
tetrachloride and acetaminophen-induced hepatotoxicity in rats. Phytother. Res., 20:997-1002, 2006
3475. Abdel-Azeem AS, Hegazy AM, Ibrahim KS, et al. Hepatoprotective, antioxidant, and ameliorative effects of
ginger Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats. J. Diet. Suppl., 10(3):195-
209, 2013
3476. Rahman IU, Khan RU, Rahman KU, et al. Lower hypoglycemic but higher antiatherogenic effects of bitter
melon than glibenclamide in type 2 diabetic patients. Nutr. J., 14:13(7 pp.), 2015
3477. Sachin BS, Monica P, Sharma SC, et al. Pharmacokinetic interaction of some antitubercular drugs with
caraway: implications in the enhancement of drug bioavailability. Hum. Exp. Toxicol., 28:175-184, 2009
3478. Park KY, Ko EJ, Kim IS, et al. The effect of evening primrose oil for the prevention of xerotic cheilitis in
acne patients being treated with isotretinoin: a pilot study. Ann. Dermatol., 26(6):706-712, 2014
3479. Koujan SE, Gargari BP, Mobasseri M, et al. Effects of Silybum marianum (L.) Gaertn. (silymarin) extract
supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized,
triple-blind, placebo-controlled clinical trial. Phytomed., 22:290-296, 2015
3480. Kashani L, Raisi F, Saroukhani S, et al. Saffron for treatment of fluoxetine-induced sexual dysfunction in
women: randomized double-blind placebo-controlled study. Hum. Psychopharm., 28:54-60, 2013
3481. Modabbernia A, Sohrabi H, Nasehi A-A, et al. Effect of saffron on fluoxetine-induced sexual impairment in
men: randomized double-blind placebo-controlled trial. Psychopharmacol., 223:381-388, 2012
3482. Shamsa A, Hosseinzadeh H, Molaei M, et al. Evaluation of Crocus sativus L. (saffron) on male erectile
dysfunction: a pilot study. Phytomed., 16:690-693, 2009
3483. Dording CM, Schettler PJ, Dalton ED, et al. A double-blind placebo-controlled trial of maca root as treatment
for antidepressant-induced sexual dysfunction in women. Evid. Based Compl. Altern. Med., 2015:#949036
(9 pp.), 2015
3484. Canevelli M, Adali N, Kelaiditi E, et al. Effects of Gingko [sic] biloba supplementation in Alzheimer's disease
patients receiving cholinesterase inhibitors: data from the ICTUS study. Phytomed., 21:888-892, 2014
3485. Patil K, Guledgud MV, Kulkarni PK, et al. Use of curcumin mouthrinse in radio-chemotherapy induced oral
mucositis patients: a pilot study. J. Clin. Diag. Res., 9(8):ZC59-ZC62, 2015
3486. Sepehri G, Derakhshanfar A, Zadeh FY. Protective effects of corn silk extract administration on gentamicin-
induced nephrotoxicity in rat. Comp. Clin. Pathol., 20:89-94, 2011
3487. Bai H, Hai C, Xi M, et al. Protective effect of maize silks (maydis stigma) ethanol extract on radiation-
induced oxidative stress in mice. Plant Foods Hum. Nutr., 65:271-276, 2010
157
3488. Lee J, Lee S, Kim S-L, et al. Corn silk maysin induces apoptotic cell death in PC-3 prostate cancer cells via
mitochondria-dependent pathway. Life Sci., 119:47-55, 2014
3489. Murata K, Takeshita F, Samukawa K, et al. Effects of ginseng rhizome and ginsenoside Ro on Testosterone
5-reductase and hair re-growth in testosterone-treated mice. Phytother. Res., 26:48-53, 2012
3490. Murata K, Noguchi K, Kondo M, et al. Inhibitory activities of Puerariae Flos against testosterone 5-
reductase and its hair growth promotion activities. J. Nat. Med., 66:158-165, 2012
3491. Kumar N, Rungseevijitprapa W, Narkkhong N-A, et al. 5-reductase inhibition and hair growth promotion of
some Thai plants traditionally used for hair treatment. J. Ethnopharm., 139:765-771, 2012
3492. Fujita R, Liu J, Shimizu K, et al. Anti-androgenic activities of Ganoderma lucidum. J. Ethnopharm., 102:107-
112, 2005
3493. Niederprum H-J, Schweikert H-U, Zanker KS. Testosterone 5-reductase inhibition by free fatty acids from
Sabal serrulata fruits. Phytomed., 1:127-133, 1994
3494. Kim Y, Son HK, Song HK, et al. Inhibition of 5-reductase activity by diarylheptanoids from Alpinia
officinarum. Planta Med., 69:72-74, 2003
3495. Hiipakka RA, Zhang H-Z, Dai W, et al. Structure-activity relationships for inhibition of human 5-reductases
by polyphenols. Biochem. Pharm., 63:1165-1176, 2002
3496. Smeriglio A, Tomaino A, Trombetta D. Herbal products in pregnancy: experimental studies and clinical
reports. Phytother. Res., 28:1107-1116, 2014
3497. Alsanad SM, Williamson EM, Howard RL. Cancer patients at risk of herb/food supplement-drug interactions:
a systematic review. Phytother. Res., 28:1749-1755, 2014
3498. Togni S, Maramaldi G, Bonetta A, et al. Clinical evaluation of safety and efficacy of Boswellia-based cream
for prevention of adjuvant radiotherpy skin damage in mammary carcinoma: a randomized placebo
controlled trial. Eur. Rev. Med. Pharmacol. Sci., 19:1338-1344, 2015
3499. Polakova K, Fauger A, Sayag M, et al. A dermocosmetic containing bakuchiol, Ginkgo biloba extract and
mannitol improves the efficacy of adapalene in patients with acne vulgaris: result from a controlled
randomized trial. Clin. Cosm. Invest. Dermatol., 8:187-191, 2015
3500. Nasiri M, Fayazi S, Jahani S, et al. The effect of topical olive oil on the healing of foot ulcer in patients with
type 2 diabetes: a double-blind randomized clinical trial study in Iran. J. Diab. Metabol. Disord., 14:38(10
pp.), 2015
3501. Khandouzi N, Shidfar F, Rajab A, et al. The effects of ginger on fasting blood sugar, hemoglobin A1c,
apolipoprotein B, apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. Iran. J. Pharm. Res.,
14(1):131-140, 2015
3502. Yamaguchi Y, Miyahara E, Hihara J. Efficacy and safety of orally administered Lentinula edodes mycelia
extract for patients undergoing cancer chemotherapy: a pilot study. Am. J. Chin. Med., 39(3):451-459, 2011
3503. Okuno K, Uno K. Efficacy of orally administered Lentinula edodes mycelia extract for advanced
gastrointestinal cancer patients undergoing cancer chemotherpay: a pilot study. Asian Pac. J. Cancer Prev.,
12:1671-1674, 2011
3504. Kim YR. Immunomodulary activity of the water extract from medicinal mushroom Inonotus obliquus.
Mycobiol., 33(3):158-162, 2005
3505. Vazquez-Ramirez R, Olguin-Martinez M, Kubli-Garfias C, et al. Reversing gastric mucosal alterations during
ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage. World
Gastroenterol., 12(27):4318-4324, 2006
3506. Wu S, Han J, Feskanich D, et al. Citrus consumption and risk of cutaneous malignant melanoma. J. Clin.
Oncol., 33(23):2500-2508, 2015
3507. Kuchta K, Schmidt M, Nahrstedt A. German kava ban lifted by court: the alleged hepatotoxicity of kava
(Piper methysticum) as a case of ill-defined herbal drug identity, lacking quality control, and misguided
regulatory politics. Planta Med., 81:1647-1653, 2015
3508. Chuang ML, Wu TC, Wang YT, et al. Adjunctive treatment with Rhodiola crenulata in patients with chronic
obstructive pulmonary disease - a randomized placebo controlled double blind clinical trial. PLoS ONE,
10(6):e0128142 [doi:10.1371/journal.pone.0128142], 2015
3509. Lukas SE, Penetar D, Su Z, et al. A standarized kudzu extract (NPI-031) reduces alcohol consumption in non
treatment-seeking male heavy drinkers. Psychopharmacol., 226(1):65-73, 2013
3510. Kusunoki M Sato D, Tsutsumi K, et al. Black soybean extract improves lipid profiles in fenofibrate-treated
type 2 diabetics with postprandial hyperlipidemia. J. Med. Food, 18(6):615-618, 2015
158
3511. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics
of acetaminophen in human volunteers. Eur. J .Drug Metab. Pharmacokin., 29(1):25-29, 2004
3512. Mahmoud BM, Ali HM, Homeida MMA, et al. Significant reduction in chloroquine bioavailability following
coadministration with the Sudanese beverages aradaib, karkadi and lemon. J. Antimicrob. Chemother.,
33:1005-1009, 1994
3513. Fakeye TO, Adegoke AO, Omoyeni OC, et al. Effects of water extract of Hibiscus sabdariffa, Linn
(Malvaceae) 'roselle' on excretion of a diclofenac formulation. Phyther. Res., 21:96-98, 2007
3514. Choi EH, Park JH, Kim MK, et al. Alleviation of doxorubicin-induced toxicities by anthocyanin-rich bilberry
(Vaccinium myrtillus L.) extract in rats and mice. Biofactors, 36(4):319-327, 2010
3515. Ashour OM, Elberry AA, Alahdal AM, et al. Protective effect of bilberry (Vaccinium myrtillus) against
doxorubicin-induced oxidative cardiotoxicity in rats. Med. Sci. Monit., 17(4):BR110-115, 2011
3516. Bansal S, Chhibber S. Phytochemical-induced reduction of pulmonary inflammation during Klebsiella
pneumoniae lung infection in mice. J. Infect. Dev. Ctries., 8(7):838-844, 2014
3517. Wu C-T, Lai J-N, Tsai Y-T. The prescription pattern of Chinese herbal products that contain dang-qui and risk
of endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan: a population-
based study. PLoS ONE, 9(12):e113887(17 pp.), 2014
3518. Asdaq SMB, Inamdar MN. Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced
myocardial damage in rat. Phytother. Res., 24:720-725, 2010
3519. Quilez AM, Saenz MT, Garcia MD. Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus
globulus Labill. interactions when administered with diazepam. Phytother. Res., 26:458-461, 2012
3520. Liu T-P, Liu I-M, Cheng J-T. Improvement of insulin resistance by Panax ginseng in fructose-rich chow-fed
rats. Horm. Metab. Res., 37:146-151, 2005
3521. Kapadia GJ, Rao GS, Ramachandran C, et al. Synergistic cytotoxicity of red beetroot (Beta vulgaris L.)
extract with doxorubicin in human pancreatic, breast and prostate cancer cell lines. J. Complement. Integr.
Med., 10(1):113-122, 2013
3522. Lim SW, Doh KC, Jin L, et al. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic
injury in an experimental mouse model. PLoS ONE, 8(8):e72685(13 pp.), 2013
3523. Al Faraj S. Antagonism of the anticoagulant effect of warfarin caused by the use of Commiphora molmol as a
herbal medication: a case report. Ann. Trop. Med. Parasitol., 99(2):219-220, 2005
3524. Van Strater ACP, Bogers JPAM. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.
Clin. Psychopharm., 27:121-123, 2012
3525. Saw JT, Bahari MB, Ang HH, et al. P[otential drug-herb interaction with antiplatelet/anticoagulant drugs.
Compl. Ther. Clin. Pract., 12:236-241, 2006
3526. Elmer GW, Lafferty WE, Tyree PT, et al. Potential interactions between complementary/alternative products
and conventional medicines in a Medicare population. Ann. Pharmacother., 41:1617-1624, 2007
3527. Carbajal R, Yisfalem A, Prandhan N, et al. Case report: bold (Peumus boldus) and tacrolimus interaction in a
renal transplant patients. Transplantat. Proc., 46:2400-2402, 2014
3528. Dasgupta A, Kidd L, Poindexter BJ, et al. Interference of hawthorn on serum digoxin measurements by
immunoassays and pharmacodynamic interaction with digoxin. Arch. Pathol. Lab. Med., 134:1188-1192,
2010
3529. Taki Y, Hagiwara E, Hirose C, et al. Effects of Ginkgo biloba extract on the pharmacokinetics and
pharmacodynamics of tolbutamide in protein-restricted rats. J. Pharm. Pharmacol., 63:1238-1243, 2011
3530. Kolding L, Pedersen LH, Henriksen TB, et al. Hypericum perforatum use during pregnancy and pregnancy
outcome. Reprod. Toxicol., 58:234-237, 2015
3531. Misaka S, Miyazaki N, Fukushima T, et al. Effects of green tea extract and (−)-epigallocatechin-3-gallate on
pharmacokinetics of nadolol in rats. Phytomed., 20:1247-1250, 2013
3532. Kissei M, Itoh T, Narawa T. Effect of epigallocatechin gallate on drug transport medicated by the proton-
coupled folate transporter. Drug Metab. Pharmacokinet., 29(5):367-372, 2014
3533. Sapmaz HI, Uysal M, Tas U, et al. The effect of lavender oil in patients with renal colic: a prospective
controlled study using objective and subjective outcome measurements. J. Altern. Compl. Med.,
21(10):617-622, 2015
3534. Bauman JE, Zang Y, Sen M, et al. Prevention of carcinogen-induced oral cancer by sulforaphane. Cancer
Prev. Res., 9(7):547-557, 2016
3535. Samojlik I, Mijatovic V, Petkovic S, et al. The influence of essential oil of aniseed (Pimpinella anisum, L.) on
drug effects on the central nervous system. Fitoterapia, 83:1466-1473, 2012
159
3536. Shahbazi F, Sadighi S, Dashti-Khavidaki S, et al. Effect of silymarin administration on cisplatin
nephrotoxicity: report from a pilot, randomized, double-blinded, placebo-controlled clinical trial.
Phytother. Res., 29:1046-1053, 2015
3537. Lua PL Salihah N, Mazlan N. Effects of inhaled ginger aromatherapy on chemotherapy-induced nausea and
vomiting and health-related quality of life in women with breast cancer. Compl. Ther. Med., 23:396-404,
2015
3538. Molto J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-
infected patients. Antimicrob. Agents Chemother., 56:5328-5331, 2012
3539. Maghsoumi-Norouzabad L, Alipooor B, Abed R, et al. Effects of Arctium lappa L. (burdock) root tea on
inflammatory status and oxidative stress in patients with knee osteoarthritis. Int. J. Rheum. Dis., 19:255-
261, 2016
3540. El-Kott AF, Bin-Meferij MM. Use of Arctium lappa extract against acetaminophen-induced hepatotoxicity in
rats. Curr. Ther. Res., 77:73-78, 2015
3541. Santos ACd, Baggio CH, Freitas CS, et al. Gastroprotective activity of the chloroform extract of the roots
from Arctium lappa L. J. Pharm. Pharmacol., 60:795-801, 2008
3542. Ferrara T, De Vincentiis G, Di Pierro F. Functional study on Boswelling phytosome as complementary
intervention in asthmatic patients. Eur. Rev. Med. Pharmacol. Sci., 19:3757-3762, 2015
3543. Marx W, McKavanagh D, McCarthy AL, et al. The effect of ginger (Zingiber officinale) on platelet
aggregation: a systematic literature review. PLoS ONE, 10(10):e0141119 (13 pp.), 2015
3544. Kumar N, Vij JC, Sarin SK, et al. Do chillies influence healing of duodenal ulcer? Br. Med. J., 288:1803-
1804, 1984
3545. Walsh Z, Gonzalez R, Crosby K, et al. Medical cannabis and mental health: a guided systematic review. Clin.
Psych. Rev., 51:15-29, 2017
3546. Manda VK, Ibrahim MA, Dale OR, et al. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica
(California poppy) and its alkaloids. Planta Med., 82:551-558, 2016
3547. Zhai X-j, Chen J-g, Liu J-m, et al. Food-drug interactions: effect of capsaicin on the pharmacokinetics of
simvastatin and its active metabolite in rats. Food Chem. Toxicol., 53:168-173, 2013
3548. Jahanbakhsh SP, Manteghi AA, Emami SA, et al. Evaluation of the efficacy of Withania somnifera
(ashwagandha) root extract in patients with obsessive-compulsive disorder: a randomized double-blind
placebo-controlled trial. Compl. Ther. Med., 27:25-29, 2016
160
CORRECTIONS
These corrections are for the early printing of the book (prior to 2013).
They have been corrected in the Kindle ebook version.
GOLDENSEAL p. 183
*Hydrastis canadensis roots/rhizome
Drug Interactions
Ia. 1) [Note CORRECTION] 3.97 gram of the root extract delivering 132 mg hydrastine and 77 mg berberine per
day for 14 days significantly INCREASED [not "reduced" as in some early copies] midazolam bioavailability in 16
healthy subjects (PO in human study).2501
GRAPEFRUIT p. 186
Citrus paradisi fruit / juice
Drug Interactions
Ia. 16) [CORRECTION: The interaction and its reference citation #2590 in the text was listed previously as number
8) with citation #1274.]
OREGON GRAPE p. 254
Mahonia spp. root bark
Contraindications
I. 5) [Note CORRECTION: This item should be listed as 3) under DRUG INTERACTIONS Ia. on the next page (p.
255). See below.]
POMEGRANATE p. 266
Punica granatum fruit
Drug Interactions
Ib. 1) A man using ezetimibe daily and rosuvastatin every other day developed rhabdomyolysis after beginning
pomegranate juice (PO in human case report).1982
HOWEVER, though pomegranate juice has been shown to inhibit CYP 3A (PO in rats, 1920 in vitro1920,1923), [Note
CORRECTION as follows.] it does not inhibit metabolism of midazolam by CYP 3A4 (PO in humans). 2213
2) [Note CORRECTION: this item is properly found as item IV. 1.]
ST. JOHN’S WORT p. 290
Hypericum perforatum herb, tops
Contraindications
I. 3) Do not take prior to surgery.1309,1890
[Note CORRECTIONS: in the last line of the first paragraph, it should read: [See drug interactions "Ib.2" below.],
not 'I.10'.
Five lines below, in the third paragraph, the brackets should read: [See drug interactions Ia.4 and Ia.7&8,
respectively.], not 'I.6 and I.8 below'.
Drug Interactions
10) [Note CORRECTION: See Ib. 7) for proper categorization.]
Appendix B
HERBAL-DRUG INTERACTIONS
[Note CORRECTIONS: In Appendices B and E in the first l00 copies of the book distributed early in 2011, asterisks
(*) are missing in front of the scientific Latin names for a number of listed herbs designated with * in the main body
of the text as containing potentially toxic compounds. (For example, European pennyroyal herb *(Mentha pulegium)
near the top of page 366 lacks an asterisk in these books.)
In Appendix B the other herbs that may be missing the * include: Aloes, Black cohosh, Cayenne, Celandine,
Chaparral, Chinese rhubarb, Cinchona, Coffee, Cubeb, Garlic, Juniper, Kava, Licorice, Madagascar periwinkle,
Sage, Sassafras, Thuja, and Valerian.]
B.4.1 Hypoglycemic and/or Antihyperglycemic Herbals p. 376
Fenugreek [Note CORRECTION: the superscript in the second line after h(t1) should be "1646", not 1645.]
B.5.1.c Warfarin or Heparin Metabolism Inhibitors and/or Anticoagulant Adjuvants p. 382
[Note CORRECTION: Cocoa seed (Theobroma cacao)1447 belongs in B.5.1.d. rather than B.5.1.c.] 88
161
CORRECTIONS (cont.)
B.5.2.b Warfarin Antagonism by Inducing Its Metabolism and/or Modifying Its Effect p. 385
Avocado fruit (Persea americana) CR3123
B.7 Modifying Enzyme Activities in Metabolic Conversions p. 387
B.7.1 Unspecified Influences of Herbal Agents on Substrate Pharmacokinetics
[Note: CORRECTION of the web address listing CYP isozyme substrates, inhibitors, and inducers is:
http://medicine.iupui.edu/clinpharm/DDIs .]
B.7.2.a Influence on CYP 1A2 Metabolic Conversion of Substrates
No Effect in Human Studies with Isoenzyme CYP 1A2 substrates p. 408
[Note CORRECTION: (SJ) St John's wort herb (Hypericum perforatum) – caffeine superscript '1328' should be
deleted, since a significant mean 26% increase in metabolite to caffeine ratio was observed in the group of 6 men
and 6 women. Also, apply this CORRECTION to Note 3.]
B.7.2.f Influence on CYP 2D6 Metabolic Conversion of Substrates
No Effect in Human Studies with Isoenzyme CYP 2D6 substrates p.426
(SJ) St John's wort herb (Hypericum perforatum) – [Note CORRECTION: debrisoquin superscript '1328' should be
deleted.] [See Note 2.]
Notes
2. [Note CORRECTION: an exception to no significant effect of St. John's wort on CYP 2D6 in human studies is a
23% increased urinary recovery ratio of debrisoquin metabolite in one study, 1328 indicative of weak induction.]
Appendix E
HERBALS AS POTENTIAL COMPLEMENTARY ADJUNCTS WITH MEDICINES
[Note CORRECTION: In Appendices B and E in the first l00 copies of the book distributed early in 2011, asterisks
(*) are missing in front of the scientific Latin names for a number of listed herbs designated with * in the main body
of the text as containing potentially toxic compounds.
In Appendix E, herbs that may be missing the * include: Black cohosh, Bryonia, Cannabis, Cayenne, Chinese
rhubarb, Cinchona, Garlic, Goldenseal, Jamaica dogwood, Licorice, Sage, Thuja, Thunder god vine, Valerian, and
Wormwood.]
E.1.1 Herbs and Those Drugs Which May Potentially Be Complemented
Cranberry fruit [NOT leaves] (Vaccinium macrocarpon) – oral hypoglycemics,3098
E.4.3 Selective Cell Retention of Drugs by Inhibiting Efflux Transport Proteins p. 500
Asian ginseng [Note CORRECTION: citation #2102 is the following: Choi CH, Kang G, Min Y-D. Reversal of P-
glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng. Planta
Med., 69:235-240, 2003.]
E.5.4. Protection from Adverse Effects by Cobalt 60 or Cesium 137 Gamma Radiation p. 504
Tulsi [Note CORRECTION: The scientific name for Tulsi, also identified as Holy basil on p. 377, is Ocimum
tenuiflorum but was formerly Ocimum sanctum.]
E.5.5 Enhancing Antineoplastic Effects of Radiation p. 504
Turmeric root (Curcuma longa) – Oc [Note CORRECTION: colorectal]2676
E.6.7 Botanicals enhancing [or reducing] the efficacy of antifungal agents p. 512
Tea (green) leaf (Camellia sinensis) [Note: CORRECTION – catechin EGCG in Tea, not in Tea tree leaf] catechin
EGCG – c/amphotericin B or fluconazole & Candida albicans2366
Tea tree leaf (Melaleuca alternifolia) f essential oil [Note: CORRECTION – catechin EGCG not in Tea tree leaf.
See above.]
Reference CORRECTIONS:
1567. WEBSITE IS NOW − http://medicine.iupui.edu/clinpharm/ddis/ClinicalTable.aspx [updated Nov. 14, 2011]
2582. Abdul MIM, Jiang X, Williams KM, et al. Pharmacokinetic and pharmacodynamic interactions of echinacea
and policosanol with warfarin in healthy subjects. Br. J. Clin. Pharmacol., 69(5):508-515, 2010
[This primary article citation replaces a secondary source.]
2590. [Previous citation was redundant.] Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the
pharmacokinetics of erythromycin. Eur. J. Clin. Pharmacol., 56:799-803, 2001
162
INDEX
ABVD, 107, 113 AE cirrhosis, 57
chemotherapy AE, 78 AE hepatotoxicity, 9, 20, 27
Acacia catechu, 120 AE steatohepatitis, 20
Acacia nilotica, 120 AE stomach damage, 19, 42
Acalypha indica, 120 AE stomach ulcers, 28
Acanthopanax koreanum, 110 alcohol abuse, 52
Acanthopanax senticosus, 35 alcohol craving, 52
acarbose, 7, 14, 29, 46, 59 alcuronium
ACE inhibitors, 105, 106 AE nausea, 41
congestive heart failure, 29 aliskiren, 84
diabetes type 2, 28 allergic asthma, 38
diabetic hypertension, 9 allergic hypersensitivity, 26, 33, 34, 35
high blood pressure, 38 Allium cepa, 44, 85, 94, 98, 113
hypertension, 39 Allium sativum, 39, 84, 85, 86, 87, 94, 98, 106,
acemetacin, 109 109, 110, 120, 123, 125
acetaminophen, 6, 24, 28, 39, 49, 54, 105, 106, allopurinol, 107
107, 110 gout, 71
AE hepatotoxicity, 18, 20, 42, 52, 58, 76 Aloe, 7, 91, 117
AE kidney toxicity, 80 Aloe barbadensis, 7
HIV neuropathic pain, 22 Aloe vera, 7, 91, 117
osteoarthritis, 11, 20, 44, 70, 77 alopecia, 74
rheumatoid arthritis, 32 alpha-reductase, 99
acetic acid, 105, 107 Alpinia galanga, 99
AE stomach ulcers, 20, 76 Alpinia officinarum, 100, 122
acne, 45 alprazolam, 72, 95
Acorus calamus, 20, 105, 112 Alstonia, 119
Actaea racemosa, 17 Alstonia scholaris, 119
acyclovir, 124 Alzheimer's disease, 13, 45
adapalene, 106 Amaranthus paniculatus, 117
acne, 45 amargo, 64
Adhatoda vasica, 120 amba, 9
adriamycin, 105, 106, 107, 112, 113, 114 American ginseng, 7, 9, 89, 98, 99, 105, 108,
breast cancer, 11 112, 114, 117
cancers, 69 American mistletoe, 101
liver carcinoma, 56 American pennyroyal, 83
Aegle marmelos, 117, 120 amikacin, 123, 124
Aesculus hippocastanum, 50, 112 aminotransferase elevations
African mistletoe, 85 AE atorvastatin, 42
Agaricus bisporus, 99 amiodarone, 48, 105
Agaricus blazei, 87 AE lung damage, 27
Agastache, 123 Amla, 9, 93, 98, 99, 105, 108, 112, 117
Agastache rugosa, 123 amlaki, 9
AIDS, 35 amoxillin, 123
Ajowan, 119 amphetamine, 108
Albizia julibrissin, 68, 86 AE fatal toxicity, 76
albuterol, 106 amphetamine toxicity
childhood asthma, 38 AE amphetamine, 76
alcohol, 19, 40, 51, 52, 63, 64, 73, 76, 80, 105, amphotericin, 124
108 amphotericin B, 105, 106, 107, 123, 124
163
candidiasis, 15, 31, 47, 60 uveitis, 78
ampicillin, 121, 122, 123 anxiety, 81
amur cork tree, 29 Apium graveolens, 120
an mole, 9 Apple, 84, 114
analgesics, 6, 107, 110 Apricot, 108
neuropathic pain, 22 Arctium lappa, 20, 105, 108
osteoarthritis, 38, 70, 77 Arctostaphylos uva-ursi, 121
anastrozole, 94 Aristolochia, 83
Andrographis, 91, 120 Aristolochia spp., 83
Andrographis paniculata, 91, 120 Arjun tree, 120
androstenedione, 99 Arjuna, 10, 105
Anemarrhena, 50 Armoracia rusticana, 120, 122
Anemarrhena asphodeloides, 50 Arnica, 11, 105, 110
Anemopsis californica, 101 Arnica montana, 11, 105, 110
anesthesia, 41 aromatase, 99
Angelica sinensis, 13, 33, 106, 115, 117, 118 Aronia melanocarpa, 27, 88, 98, 99, 105, 112,
angina pectoris, 81 113
angiotensin II receptor antagonists, 106 arteether, 107
hypertension, 39 Plasmodium berghei, 79
angiotensin receptor blockers, 106 Artemisia absinthium, 101
congestive heart failure, 29 Artemisia annua, 71, 107
aniline, 93 Artemisia douglasiana, 101
Anise, 10 Artemisia dracunculus, 83
ankle sprain, 11 artemisinin, 107
ankylosing spondylitis, 74 Plasmodium faciparum, 79
antacids, 25 arthritis, 70
Anthemis nobilis, 64 Asarabacca, 83
antibiotics, 106 Asarum canadensis, 83
bacterial resistance, 48 Asarum europeum, 83
diabetic foot ulcer, 58 ascorbate, 103
anticholinergics, 105 ascorbic acid, 103
multiple sclerosis, 23 Ashwagandha, 11, 108, 112, 114, 122, 124
overactive bladder, 23 Asian ginseng, 12, 94, 99, 105, 108, 112, 114,
anticoagulants, 32, 106 117
congestive heart failure, 29 Asparagus, 92
anticonvulsants, 105 Asparagus officinalis, 92
HIV neuropathic pain, 22 aspirin, 28, 44, 107, 110
neuropathic pain, 22 AE stomach damage, 26
antidepressants, 10, 105 AE stomach ulcers, 73, 76
neuropathic pain, 22 ischemic stroke, 66
antiherpetics, 107 osteoarthritis, 70
uveitis, 78 asthma, 17, 38
antihistamines, 107 Astragalus, 13, 105, 114, 118
COPD, 75 Astragalus membranaceus, 13, 33, 105, 114,
antihypertensives, 106 118
diabetes type 2, 28 Astragalus mongholicus, 13
anti-inflammatory drugs atazanavir, 24, 93
neuropathic pain, 22 atenolol, 106
antiplatelet drugs, 44 high blood pressure, 58
diabetes type 2, 28 atorvastatin, 93, 106, 107
antitoxoplasmic drugs, 107 AE aminotransferase elevations, 42
164
cardiotoxicity, 40 Bibhitaki, 120, 121
high cholesterol, 42 biguanides, 36, 87
inflammation, 72 Bilberry, 15, 105, 122
auditory hair cell damage bioavailability
AE cisplatin, 13, 52 curcumin, 19, 55
augmentin, 107 EGCG, 19, 55
COPD exacerbation, 61 emodin, 19
auranofin, 107 Bishop's weed, 108
rheumatoid arthritis, 74 Bitter leaf, 85
Avena sativa, 58 Bitter melon, 16, 87, 101
Avocado, 89 Bitter orange, 16, 94
Azadirachta indica, 117 bitterwood, 64
bacitracin, 122 Black cherry, 120
baclofen, 105 Black cohosh, 17
multiple sclerosis, 23 Black cumin, 17, 91, 105, 108, 110, 124
bacterial resistance, 48 Black horehound, 124
Bael, 117, 120 Black nightshade, 120
Ballota nigra, 124 Black pepper, 18, 85, 94, 105, 108
Barbary wolfberry, 55 Black raspberry, 19, 91, 93, 98, 100, 108, 114,
Barberry, 14, 85, 92, 94, 96, 97, 99, 100, 105, 118
108, 122, 123 black Sampson, 33
barbiturates, 21 black tea, 109, 114, 118
Basil, 83 Black walnut, 91, 98, 100
BCNU Blackberry, 108
tumor cells, 28 bladder cancer, 79
beclomethasone, 105, 106 Bladderwrack, 88
asthma, 17, 38 bleeding disorders, 43
Beet, 112 Bloodroot, 118
bei wu wei zi, 67 Blueberry, 84, 91, 92, 94, 96, 97, 99, 100
Beilschmiedia cinnamomea, 120, 121 Boldo, 19
Belleric myrobalan, 108 Borage, 19, 83, 108
benign prostatic hyperplasia, 66 Borago officinalis, 19, 83, 108
Benincasa hispida, 109 bortezomib, 112
benzo[a]pyrene, 91 Boswellia serrata, 37, 106, 110, 117
benzodiazepine Boswellia spp., 94
AE withdrawal, 50, 61, 81 brain damage
benzodiazepines, 106, 107, 108 AE ethanol, 37
berberine, 123 Brassica nigra, 121, 122
Berberis spp., 85, 123 Brassica oleracea, 91, 92, 98, 112
Berberis vulgaris, 14, 92, 94, 96, 97, 99, 100, Brassica oleracea v. acephala, 98, 100
105, 108, 122 Brassica oleracea v. italica, 98, 99, 118
Beta vulgaris, 112 Brassica oleracea var. italica, 114
beta-agonists, 105 Brassica spp., 32, 91, 92, 106, 112, 114
asthma, 17, 38 breast cancer, 7, 11, 48, 67, 79
beta-blockers, 105, 106 breast cancer cells, 9
congestive heart failure, 29 breast cancer cells, 73
diabetes type 2, 28 breast cancer cells, 74
diabetic hypertension, 9 breast cancer survivors, 17
hypertension, 39 breast feeding, 101
beta-hydroxysteroid dehydrogenase, 100 Broccoli, 98, 99, 112, 114, 118
Bibhitakhi, 112 Brussels sprouts, 98, 112
165
budesonide, 106, 107 cancers, 69
asthma, 38 cardiac glycosides, 49
COPD, 61 cardiotoxicity
bumetanide, 104 AE doxorubicin, 10, 15, 18, 31, 32, 40, 48,
bupropion, 91 55, 60
Burdock, 20, 105, 108 Carduus marianus, 57
buspirone, 72, 93, 96 Carica papaya, 85
button mushroom, 99 carmustine
Cabbage, 98, 112 tumor cells, 28
Caesalpinia sappan, 122 Carthamus tinctorius, 100
Caffea arabica, 99 Carum carvi, 23
caffeine, 92 Carum copticum, 119
Calamus, 20, 105, 112 Cassia, 23, 87, 120, 121
calcein-AM, 85 Cat’s claw, 24, 94, 105, 113, 117
calciferol, 103 Catechu, 120
calcium, 85, 103, 105, 106 Catha edulis, 122
mineral absorption, 19, 25, 27, 42, 55 Cayenne, 24, 85, 87, 105
calcium channel blockers, 105, 106 CCNU, 107, 113
diabetic hypertension, 9 chemotherapy AE, 78
hypertension, 39 cefaclor, 85
California mugwort, 101 Celandine, 25, 120
California poppy, 91, 92, 94 celecoxib, 107, 110
Calluna vulgaris, 118 gout, 71
Camellia sinensis, 72, 84, 85, 91, 92, 94, 96, 97, osteoarthritis, 70, 77
98, 99, 100, 107, 109, 110, 114, 118, Celery, 120
121, 122, 123, 124 celiprolol, 85
camptothecin, 106, 112 Centella asiatica, 120
prostate cancer cells, 31 cerebral edema
cancer cells AE irradiation, 37
breast, 9, 73, 74 Chaga, 25, 105
cancer chemoprevention, 72 Chamaemelum nobile, 26, 64, 65
cancer-related fatigue, 8, 48 Chamomile, 25, 105, 112, 113, 120, 121
cancers, 69 Chaparral, 100, 109, 110, 120
candidiasis, 15, 31, 47, 60 Chelidonium majus, 25, 120
cannabis, 99 chemotherapy, 105, 112, 113
Cannabis, 21, 105, 108, 110 AE cardiotoxicity, 55
Cannabis indica, 21, 94 AE fatigue, 8, 48
Cannabis sativa, 21, 94, 99, 105, 108, 110 AE leukopenia, 15
capecitabine, 112 AE nausea, 41
capsaicin AE nausea & vomiting, 62
AE hyperalgesia, 22 AE oral mucositis, 26, 39, 79
Capsicum annuum, 109 AE vomiting, 21
Capsicum anuum, 26, 84 cancers, 69
Capsicum frutescens, 24, 85, 87, 105 nausea & vomiting, 41
captopril, 10, 106 chemotherapy AE, 78
heart damage, 40 cherry, 71
hypertension, 40 Chicory, 120
CAR, 90, 92 childhood asthma, 38
Caraway, 23 chile, 26
carboplatin, 107, 113 Chili, 26, 84, 109
AE oral mucositis, 79 chili pepper, 26
166
chilli, 26 AE kidney damage, 34, 58
Chinese hibiscus, 27 AE nausea & vomiting, 41
Chinese knotweed, 37 AE neuropathic pain, 26
Chinese lantern tree, 120, 121 AE oral mucositis, 79
Chinese licorice, 50 AE peripheral neuropathy, 46
Chinese raisin tree, 109 AE weight loss, 34
Chinese rhubarb, 27, 84, 86, 120, 121 cancers, 69
Chinese skullcap, 27, 91, 109, 120 chemotherapy AE, 78
Chinese wolfberry, 55 gastric cancer, 13
Chirata, 87 HNSCC, 79
chlorambucil, 106, 113 liver cancer cells, 10
AE oral mucositis, 39 liver carcinoma, 56
chloramphenicol, 122, 123 lung cancer cells, 10
chlorhexidine, 122, 123 prostate cancer cells, 31
chloromycetin systemic inflammation, 79
bacterial resistance, 48 Citrus, 98
chloropropamide, 75, 87 Citrus aurantium, 16, 94
chloroquin, 106 Citrus grandis, 94
rheumatoid arthritis, 32 Citrus paradisi, 48, 82, 91, 94
chloroquine, 49, 106, 122 Citrus sinensis, 84, 121
malaria, 52 Citrus spp., 98
chlorpromazine clarithromycin, 80, 107
schizophrenia, 45 Clary sage, 120, 122
chlorzoxazone, 93 clindamycin, 123
Chokeberry, 27, 88, 98, 99, 105, 112, 113 clomiphene, 106
chorhexidine, 40, 106, 123 polycystic ovary syndrome, 56
chromosomal damage Clostridium tetani, 53
AE cyproterone, 76 clotrimazole, 124
chronic bacterial prostatitis, 66, 73 Clove, 28, 98, 105, 109, 110, 120, 122, 124
chronic pain, 22 clozapine, 70
Cichorium intybus, 120 schizophrenia, 45
cigarette smoking, 54 cocaine, 108
Cimicifuga racemosa, 17 AE hyperactivity, 8, 13
Cinchona, 28 AE locomotor activity, 15, 30, 47, 60
Cinchona spp., 28 Coccinia grandis, 87
Cinnamomum aromaticum, 23 Coccinia indica, 87
Cinnamomum cassia, 23, 87, 120, 121 Cocoa, 28, 88, 106, 118
Cinnamomum spp., 122 Coconut, 110
Cinnamomum verum, 28, 120, 121 Cocos nucifera, 110
Cinnamomum zeylanicum, 28 codeine, 10, 21, 61, 105, 110
Cinnamon, 28, 120, 121, 122 neuropathic pain, 22
Cinnamon beilschmiedia, 120, 121 Coffea arabica, 114, 118
ciprofloxacin, 106, 107, 122, 123 Coffee, 99, 114, 118
chronic bacterial prostatitis, 73 Cola, 29, 106, 122
COPD, 34 Cola acuminata, 29
E. coli, 29 Cola nitida, 29, 106, 122
cirrhosis colchicine, 107
AE ethanol, 57 gout, 71
cisplatin, 105, 106, 107, 112, 113, 115 Coleus, 91, 92, 94, 96, 98, 124
AE auditory hair cell damage, 13, 52 Coleus forskohlii, 91, 92, 94, 96, 98, 124
AE hepatotoxicity, 32 colorectal cancer, 67
167
colorectal cancer cells, 9, 80 Curcuma domestica, 77
combflower, 33 Curcuma longa, 26, 77, 85, 91, 92, 94, 96, 97,
Comfrey, 83 98, 107, 109, 110, 112, 113, 114, 115,
Commiphora mukul, 49, 92 118, 121, 122
Common groundsel, 83 Curcuma xanthorrhiza, 113
congestive heart failure, 29 curcumin, 107
constitutive androstane receptor, 90, 92 bioavailability, 19, 55
COPD, 61, 75 Plasmodium falciparum, 71
COPD, 34 cyanocobalamine, 103
COPP, 107, 113 cyclophosphamide, 105, 106, 107, 112, 113,
chemotherapy AE, 78 115
Coptis, 29, 85, 92, 94, 96, 97, 99, 100, 106, 109, AE DNA damage, 8
122, 123 AE fatigue, 48
Coptis chinensis, 29, 85, 109, 123 AE immunosuppression, 9, 25
Coptis groenlandica, 29 AE mutations, 9
Coptis spp., 92, 94, 96, 97, 99, 100, 106, 122 AE nausea, 41
Cordyceps, 124 AE nausea & vomiting, 41
Cordyceps sinensis, 124 AE testicular toxicity, 49
Coriander, 109, 110, 120, 123 breast cancer, 11, 67
Coriandrum sativum, 109, 110, 120, 123 cancers, 69
Coriolus versicolor, 96 lung carcinoma, 34, 35
Corn silk, 31, 106, 112, 117 lung carcinoma cells, 8
corticosteroid melanoma cells, 8
allergic asthma, 38 ovarian cancer cells, 8
corticosteroids, 105, 107, 110 systemic inflammation, 78, 79
asthma, 38 cycloplegics, 107
COPD, 75 uveitis, 78
mustard gas inhalation, 17 cyclosporine, 14, 30, 41, 44, 47, 59, 85, 105
corticosterone AE pancreatic injury, 13
edema, 50 Cymbopogon citratus, 100
inflammation, 50 CYP 19, 99
cortisol, 5, 48, 53, 93, 100 CYP27A1, 100
Corynanthe yohimbe, 81 cyproterone, 107
Cotton, 99 AE chromosomal damage, 76
COX-2 inhibitors cysteamine
osteoarthritis, 38 AE stomach ulcers, 36
Cranberry, 31, 85, 91, 94, 96, 98, 106, 112, Cytisus scoparius, 67, 109
113, 114, 117, 124 cytoxan
Crataegus laevigata, 109 breast cancer cells, 9
Crataegus monogyna, 109 dacarbazine, 107, 113
Crataegus spp., 49, 106 cancers, 69
Crigler-Najjar syndrome, 14, 59 Damiana, 99
Crocus sativa, 107 dan shen, 92, 93, 94, 96
Crocus sativus, 65, 100, 109 Dan shen, 32, 84, 97
Crotalaria spp., 83 darunavir, 35, 94
Crucifers, 32, 91, 92, 98, 106, 112, 114 daunorubicin, 85, 113, 114
cuassia, 64 debrisoquin, 97
Cumin, 114 dehydroepiandosterone, 90
Cuminum cyminum, 114 depression, 78
Curcuma aromatica, 77, 91, 92, 94, 96, 97, 98, desogestrel, 69
107, 110, 112, 113 dexamethasone, 106, 107
168
AE osteoporosis, 45 high blood pressure, 58
cerebral edema, 37 doxorubicin, 61, 85, 105, 106, 107, 112, 113,
chemo nausea & vomiting, 61 114
nausea, 41 AE cardiotoxicity, 10, 15, 18, 31, 32, 40, 48,
nausea & vomiting, 42 55, 60
dexlansoprazole, 104 AE fatigue, 48
dextromethorphan, 14, 16, 30, 47, 59, 92, 97 AE hematopoietic damage, 16
dextropropoxyphene, 105 AE leukopenia, 24
neuropathic pain, 22 AE mycardial damage, 16
diabetes, 12, 16, 70, 87 AE nausea & vomiting, 41
diabetes type 2, 28, 32, 37, 39, 42, 57, 63, 78 AE testicular toxicity, 56
diabetic foot ulcer, 58 breast cancer cells, 9
diarrhea, 37 liver cancer cells, 10
diazepam, 10, 24, 36, 93, 97 lung cancer cells, 10
Dichrostachys glomerata, 120, 121 dysmenorrhea, 37
diclofenac, 50, 62, 96, 105, 106, 107, 110 Echinacea, 33, 86, 91, 94, 106
alopecia, 74 Echinacea angustifolia, 33, 106
arthritis, 70 Echinacea pallida, 34, 106, 113
osteoarthritis, 70 Echinacea purpurea, 34, 35, 86, 91, 94, 98,
rheumatoid arthritis, 18, 66, 78 112
dicofenac edema, 50
renal colic, 35 efavirenz, 44, 93
dienogesterol, 69 EGCG, 105, 106
digitalis, 85 bioavailability, 19, 55
digoxin, 8, 13, 14, 30, 35, 47, 59, 85, 86 Ehrlich ascites carcinoma
heart failure, 10, 49 ifosfamide, 18
dihydrocodeine, 105 Eleuthero, 35
neuropathic pain, 22 Eleutherococcus senticosus, 35
Dioscorea villosa, 81 Embelia ribes, 121
dipeptidyl peptidase-4 inhibitors, 7 Emblica officinalis, 9, 93, 98, 105, 108, 112, 117
Dipteryx odorata, 99 emodin, 105
Dipteryx oppositifolia, 99 bioavailability, 19
diuretics, 106 enalapril, 10, 105, 106
congestive heart failure, 29 kidney fibrosis, 13, 33
heart failure, 10 English lavender, 35, 92, 94, 96, 97, 106
hypertension, 39 English plantain, 36, 106, 110
DNA damage Epimedium grandiflorum, 99
AE cyclophosphamide, 8 Epimedium macranthum, 99
docetaxel, 94, 106, 107, 112, 113, 115 epirubicin, 85, 105, 106, 107, 112, 113, 114
AE nausea, 41 AE nausea, 41
lung cancer, 80 breast cancer, 11, 67
metastatic prostate cancer, 63 Equisetum spp., 101
prostate cancer cells, 63 erectile dysfunction
systemic inflammation, 79 AE fluoxetine, 65
Dog rose, 32, 106 erlotinib, 112
donepezil, 105, 106 erythrocycin, 122
Alzheimer's disease, 13, 45 erythromycin, 48, 67, 93, 122
Dong quai, 33, 106, 115, 117, 118 Eschscholtzia californica, 92, 94
dorzolamide, 107 Eschscholzia californica, 91, 94
glaucoma, 65 esomeprazole, 103, 104
doxazosin, 106 estradiol, 91, 99, 100
169
estrone, 99, 100 Flax, 114
ethacrynic acid flouracil, 106, 113
tumor cells, 28 AE nausea, 41
ethambutol, 105, 106, 122, 123 fluconazol, 123, 124
tubercular lymphadenitis, 40 fluconazole, 123, 124
tuberculosis, 11 fluoropyrimidine, 112
ethanol, 21, 105 fluoroquinolone
AE brain damage, 37 E. coli, 29
AE gastric ulcers, 64 fluorouracil, 9, 31, 105, 106, 107, 112
AE hepatotoxicity, 9, 19, 20, 27, 37, 52, 57, AE fatigue, 48
63, 64, 80 breast cancer, 11
AE liver damage, 10 colorectal cancer, 68
AE steatohepatitis, 20 gastric cancer, 13, 68
AE stomach damage, 19, 40, 42 GI cancer, 67
AE stomach ulcer, 63 liver carcinoma, 56
AE stomach ulcers, 18, 20, 26, 28, 49, 54, 73, fluoruracil, 78, 113, 115
76 chemotherapy AE, 78
ethanolic extract, 72 systemic inflammation, 79
ethinylestradiol, 69, 106 fluoxetine, 10, 107
AE hepatotoxicity, 53 AE erectile dysfunction, 65
etoposide, 106, 107, 112, 113, 114, 115 AE sexual dysfunction, 65
cancers, 69 depression, 78
prostate cancer cells, 31 flurbiprofen, 96, 97
systemic inflammation, 79 fluticasone, 105, 106
etravirine, 94 allergic asthma, 38
Eucalyptus, 36, 94, 120 asthma, 17, 38
Eucalyptus globulus, 94, 120 Foeniculum vulgare, 83
Eucalyptus spp., 36 folate, 107
Eugenia caryophyllata, 28 GI cancer, 67
Eugenia jambolana, 87 folic acid, 73, 105
Eupatorium purpureum, 83 rheumatoid arthritis, 18
Euphorbia characias, 123 formoterol, 106
European pennyroyal, 83 asthma, 38
Evening primrose, 36, 106 Foti, 99
ezetimibe, 62 Fo-ti, 37
Fanconi syndrome Fragaria spp., 91, 98, 100, 109
AE ifosfamide, 18 Frankincense, 37, 94, 106, 110, 117
fatigue, 48 French maritime pine, 38, 106, 110, 113
felodipine, 16 Fucus vesiculosus, 88
Fennel, 83 Fu-lin, 50
fenofibrate, 107 furosemide
hyperlipidemia, 68 heart failure, 10
fenoterol, 107 gabapentin
COPD, 61 HIV neuropathic pain, 22
Fenugreek, 36, 87, 91, 106, 109, 110 Galangal, 44
ferrous sulfate, 26, 104 galantamine, 105, 106
fetotoxins, 101 Alzheimer's disease, 13, 45
Feverfew, 101 Ganoderma lucidum, 100, 113, 114, 115, 118
fexofenadine, 32, 84, 85, 86 Garcinia mangostana, 99
fexofenodine, 85 Garden cress, 91
finasteride, 69, 93 Garlic, 39
170
Garlic, 84, 85, 86, 87, 94, 98, 106, 109, 110, Goldenseal, 46, 85, 92, 94, 96, 97, 99, 100, 106,
120, 123, 125 109, 120, 122, 123
gastric cancer, 13, 67 Gossypium herbaceum, 99
gastric ulcers Gossypium hirsutum, 99
AE indomethacin, 64 Gotu kola, 120
gemcitabine, 105, 107, 112 gout, 71
bladder cancer, 79 granisetron, 106
pancreatic cancer, 18 nausea, 41
gemicitabine, 107, 113 granistron, 107
chemotherapy AE, 78 chemo nausea & vomiting, 61
genotoxicity Grape, 109
AE mitomycin C, 8 Grape seed, 88, 118
genotoxins, 101 Grapefruit, 48, 91, 94
gentamicin, 105, 106, 122, 123, 124, 125 Grapes, 92, 94, 96, 97, 99, 118
AE kidney toxicity, 12, 18, 31, 40 Gravel root, 83
AE ototoxicity, 46 Graves' disease, 45
Gentian, 125 Greater galangal, 99
Gentiana lutea, 125 green tea, 84, 91, 92, 94, 98, 99, 107, 112, 114,
Geranium, 123 118, 123
Germander, 83 Grifola frondosa, 56, 87, 106, 123
GI bleeding, 88 GSTs, 98
GI cancer, 67 guabo, 64
Gilbert’s syndrome, 14, 59 Guarana, 48, 106
Ginger, 40, 85, 88, 94, 99, 106, 109, 110, 113, Guggul, 49, 92
118 Gulancha, 10, 87, 117
Ginkgo, 43, 85, 86, 88, 91, 92, 94, 96, 97, 98, Gymnema, 87
106, 113, 117, 118, 125 Gymnema sylvestre, 87
Ginkgo biloba, 43, 85, 86, 88, 91, 92, 94, 96, 97, Gynostemma, 87
98, 106, 113, 117, 118, 125 Gynostemma pentaphyllum, 87
ginseng, 94, 108, 112, 117 haliilaj, 9
ginsenosides, 99 haloperidol
glatiramer, 105 schizophrenia, 45
multiple sclerosis, 23 Haritaki, 120, 122
glibenclamide, 7, 23, 63, 75, 84, 87 Hawthorn, 49, 106, 109
diabetes type 2, 57, 63 he shou wu, 37
gliclazide, 23, 28, 87 heart damage
glipizide, 75, 87 AE isoproterenol, 46, 76
glucosamine, 105 heart disease, 81
osteoarthritis, 20 heart failure, 10, 49
glutathione S-transferases, 98 Heather, 118
glyburide, 7, 63, 87 Hedeoma pulegoides, 83
diabetes type 2, 63 Helicobacter pylori dyspepsia, 18
Glycine max, 68, 85, 94, 99, 100, 107, 113, 114, heliotherapy, 116
117, 118 hematopoietic damage
Glycyrrhia uralensis, 86 AE doxorubicin, 16
Glycyrrhiza glabra, 53, 85, 99, 100, 106, 110, hemolytic anemia, 14, 29, 59
113 heparin, 88
Glycyrrhiza uralensis, 50, 53, 99, 100, 106, 120 hepatotoxicity, 25
goji, 55 AE acetaminophen, 18, 20, 42, 52, 58, 76
Goji, 106, 113, 118 AE alcohol, 9, 27
AE cisplatin, 32
171
AE ethanol, 10, 19, 20, 27, 37, 40, 52, 57, 63, hypertensive diabetics, 9
64, 73, 80 hypoglycemic drugs, 12
AE ethinylestradiol, 52 hypoglycemic herbs, 86
AE isoniazid, 10, 76, 78, 80 ibuprofen, 106, 107, 110
AE meloxicam, 76 AE stomach ulcers, 54
AE pyrazinamide, 10, 76, 78, 80 dysmenorrhea, 37
AE rifampicin, 10, 52, 76, 78, 80 osteoarthritis, 37, 70
AE trabectidin, 32 ifosfamide, 105, 107, 113
hexobarbital, 50 AE Fanconi syndrome, 18
HIBISCUS, 49 AE kidney damage, 18
Hibiscus rosa-sinensis, 27 cancers, 69
Hibiscus sabdariffa, 49 Ehrlich ascites carcinoma, 18
high blood pressure, 38, 40, 58, 81 Illicium verum, 121, 123
high cholesterol, 15, 30, 42, 47, 60 imatinib, 12
Hippophae rhamnoides, 110, 117 imipenem, 122
HIV infection, 35 imipramine, 10
HIV neuropathic pain, 22 immune suppressants, 107
HNSCC tumors, 79 uveitis, 78
holy basil, 75 immunosuppressant
hombre grande, 64 AE isoniazid, 76, 80
homoharringtonine, 85, 113, 114 AE pyrazinamide, 76, 80
hong jing tian, 75 AE rifampicin, 76, 80
Hops, 50, 81, 99, 106, 113 immunosuppression
Horny goat weed, 99 AE cyclophosphamide, 9, 25
Horse chestnut, 50, 112 indapamide, 104
Horseradish, 120, 122 Indian gooseberry, 9
Horsetail, 101 Indian nettle, 120
Hovenia dulcis, 109 Indian stinging-nettle, 87
Humulus lupulus, 50, 81, 99, 106, 113 indomethacin, 73, 105, 106, 107, 110
Hydrastis canadensis, 46, 85, 92, 94, 96, 97, 99, AE gastric ulcers, 64
100, 106, 109, 120, 122, 123 AE stomach ulcers, 28, 36
hydrochloric acid gout, 71
AE gastric ulcers, 64 migraine headache, 70
hydrochlorothiazide, 106 stomach ulcers, 54
high blood pressure, 58 inflammation, 50, 72
hydrochoric acid, 107 influenza, 8
hydrocortisone, 109 influenza vaccine, 105, 106
hydroxycamptothecin, 85, 113, 114 influenza, 8
hydroxychloroquine, 105, 107 respiratory disorders, 33
rheumatoid arthritis, 18, 63 respiratory symptoms, 8
hydroxyethyl salicylate, 105 Inonotus obliquus, 25, 105
ankle sprain, 11 insulin, 14, 29, 46, 59, 86
hyperactivity diabetes type 2, 28
AE cocaine, 8, 13 interferon beta, 105
AE methamphetamine, 8, 13 multiple sclerosis, 23
hyperalgesia intestinal damage
AE capsaicin, 22 AE meloxicam, 76
Hypericum perforatum, 17, 69, 84, 94, 96, 107, ipratropiumbromide, 107
109, 117 COPD, 61
hyperlipidemia, 68 irinotecan, 69, 94, 107, 112, 113
hypertension, 39 cancers, 69
172
colorectal cancer, 67 Larix spp., 53, 106, 124
GI cancer, 67 Larrea tridentata, 100, 109, 110, 120
iron, 26, 84, 85, 104, 105, 106 latanoprost, 105, 106
mineral absorption, 19, 25, 27, 42, 55 ocular hypertension, 15, 38
irritable bowel, 26 Lavandula angustifolia, 35, 92, 94, 96, 97
ischemic stroke, 66 Lavandula officinalis, 35, 106
isoniazid, 105, 106, 107, 122, 123 Lavandula vera, 35
AE hepatotoxicity, 10, 76, 78, 80 lavender, 92, 94, 96, 97
AE immunosuppressant, 76, 80 L-dopa, 106
tubercular lymphadenitis, 40 Parkinson's disease, 37
tuberculosis, 11 leflunomide, 106, 107
isoniazide, 23 rheumatoid arthritis, 32, 66
isoproterenol, 106, 107 Lemon balm, 109
AE heart damage, 40, 46, 76 Lemongrass, 100
isosorbide dinitrate, 10, 105 Lentinula edodes, 67, 100, 107, 112
isotretinoin, 106 Lentinus edodes, 67, 107
AE xerotic cheilitis, 36 Leonurus cardiaca, 124
Ivy gourd, 87 Leopoldia comosa, 124
Jambolan, 87, 109, 117 Lepidium meyenii, 56, 106
Japanese ginseng, 100 Lepidium sativum, 91
jaundice, 14, 29, 46, 51, 59 Leptospermum scoparium, 123
Juglans nigra, 91, 98, 100 Lesser galangal, 100, 122
Jujube, 50 letrozole, 94
Kale, 98, 100 leukopenia
kanamycin, 124 AE chemotherapy, 15
Kava, 50, 91, 94, 114 AE doxorubicin, 24
ketoconazole, 14, 30, 47, 59, 85, 123, 124, 125 levofloxacin, 106, 122
ketoprofen, 107, 110 E. coli, 29
osteoarthritis, 70 levofolinate, 107
Khat, 122 colorectal cancer, 68
kidney damage Licorice, 53, 85, 86, 99, 100, 106, 110, 113, 120
AE cisplatin, 34, 58 Ligusticum chuanxiong, 50
AE ifosfamide, 18 linezolid, 122
kidney dysfunction, 81 Linum usitatissimum, 114
kidney fibrosis, 13, 33 lisinopril, 106
kidney toxicity high blood pressure, 58
acetaminophen, 80 Little ironweed, 109
AE gentamicin, 12, 18, 31, 40 Little ironwood, 98
Kikar, 120 liver cancer cells, 10
Kino, 87 liver carcinoma, 56
Korean acanthopanax, 110 liver disease, 81
Krameria triandra, 118 liver disorders, 51
Kudzu, 52, 94, 100, 106, 109, 113 liver dysfunction, 17
Kutaki, 52, 106, 109, 110, 120, 122 liver-toxic drugs, 51
LABA, 107 Lobelia, 54, 85, 109
COPD, 75 Lobelia inflata, 54, 85, 109
LAMA, 107 locomotor activity
Laminaria japonica, 88 AE cocaine, 15, 30, 47, 60
Laminaria saccharina, 88 Long pepper, 55, 85, 94, 106, 117
lansoprazole, 103, 104 lopinavir, 94
Larch, 53, 106, 124 losartan, 14, 30, 47, 57, 59, 96
173
lovastatin, 15, 30, 47, 58, 60 metformin, 7, 14, 23, 28, 29, 39, 46, 59, 69, 87,
lung cancer, 80 106
lung cancer cells, 10, 80 diabetes type 2, 28, 37, 57
lung carcinoma, 34, 35 methadone, 84, 93, 105
lung carcinoma cells, 8 neuropathic pain, 22
lung damage methamphetamine
AE amiodarone, 27 AE hyperactivity, 8, 13
lung infection, 80 methotrexate, 73, 105, 106, 107, 113, 115
lung metastasis, 79 AE vomiting, 21
Lycium, 55, 88, 106, 113, 118 ankylosing spondylitis, 74
Lycium barbarum, 55, 88, 106, 113, 118 breast cancer cells, 9
Lycopersicon esculentum, 113, 117 rheumatoid arthritis, 18, 32, 63, 74
ma kham pom, 9 systemic inflammation, 79
Maca, 56, 106 metoclopramide, 107
magnesium, 104 chemo nausea & vomiting, 61
Magnolia, 115, 118, 120 nausea & vomiting, 41
Magnolia officinalis, 115, 118, 120 metolazone, 104
Mahonia aquifolium, 100, 109 metoprolol, 97
Mahonia spp., 59, 85, 92, 94, 96, 97, 99, 107, metronidazole, 125
123, 124 midazolam, 10, 12, 14, 29, 32, 34, 35, 43, 46,
Maitake, 56, 87, 106, 123 59, 61, 62, 67, 68, 93, 94, 95
Ma-kombu, 88 migraine headache, 70
Malabar nut, 120 Milk thistle, 57, 84, 85, 87, 91, 94, 96, 98, 106,
Malus domestica, 84, 114 109, 110, 112, 113, 114, 117, 118, 125
mangosteen, 99 mineral absorption, 19, 25, 27, 42, 55
Manuka, 123 minoxidil, 107
Matricaria chamomilla, 25 alopecia, 74
Matricaria recutita, 25, 26, 65, 105, 112, 113, Mirabolano emblico, 9
120, 121 mitomycin C, 105, 106, 112, 113
MDR AE genotoxicity, 8
definition, 119 AE myelosuppression, 56
Mediterranean spurge, 123 colorectal cancer, 68
mefenamic acid, 106 mitoxantrone, 85, 106, 113, 114
dysmenorrhea, 37 AE oral mucositis, 39
Melaleuca alternifolia, 74, 107, 123, 124 Momordica charantia, 16, 87, 101
melanoma cells, 8 Mongolian mulberry, 121
Melilotus officinalis, 98 MOPP, 107, 113
Melissa officinalis, 109 chemotherapy AE, 78
meloxicam, 107 Moringa, 87
AE hepatotoxicity, 76 Moringa oleifera, 87
AE intestinal damage, 76 Moroccan thyme, 123
AE stomach ulceration, 76 morphine, 105, 106, 110
memantine, 105 AE morphine dependence, 12
Alzheimer's disease, 13 AE opioid withdrawal, 74
Mentha piperita, 61, 86, 94, 99, 109, 123, 124 AE withdrawal, 12, 65, 70
Mentha pulegium, 83 chronic pain, 22
Mentha spicata, 61, 113 neuropathic pain, 22
Mentha x piperita, 107, 113, 117 pain, 42
metamizol, 110 morphine dependence
metastatic prostate cancer, 63 AE morphine, 12
Morus alba, 85, 113
174
Morus mongolica, 121 nicardipine, 85, 93
Morus spp., 92, 94, 96, 97 nicotine, 107, 108
Motherwort, 124 AE reduced testosterone and sperm, 70
motor vehicle, 21, 50 nifedipine, 10, 12, 43, 93, 95, 106
MRP1, 111 high blood pressure, 58
MRP2, 111 high blood pressure, 38
MRSA Nigella sativa, 17, 91, 105, 108, 110, 124
definition, 119 nitrendipine, 62, 93
Mulberry, 85, 92, 94, 96, 97, 113 norfloxacin, 122, 123
multiple sclerosis, 23 northern schisandra, 67
mushroom, 87 novobiocin, 122
Mustard, 121, 122 NSAID
mustard gas inhalation, 17 AE intestinal damage, 76
Mutagens, 101 AE stomach ulceration, 76
mutations dysmenorrhea, 37
AE cyclophosphamide, 9 NSAIDs, 6, 105, 106, 107, 110
mydriatics, 107 AE stomach ulcers, 54
uveitis, 78 chronic pain, 22
myelosuppression HIV neuropathic pain, 22
AE mitomycin C, 56 neuropathic pain, 22
myocardial damage osteoarthritis, 38, 70, 77
AE doxorubicin, 16 rheumatoid arthritis, 32, 63, 74
Myristica fragrans, 91 uveitis, 78
Myrtle, 123 nursing mothers, 101
Myrtus communis, 123 Nutmeg, 91
N-acetyl cysteine, 9, 105, 114 nystatin, 124
nadolol, 73, 84 Oat, 58
nan wu wei zi, 68 OATP, 84
Nan wu wei zi, 85, 113 obsessive-compulsive disorder, 11
naproxen, 77, 107, 110 OCD, 11
osteoarthritis, 70 Ocimum basilicum, 83, 117
narrow-leaved coneflower, 33 Ocimum gratissimum, 98, 109, 110, 114
Nasturtium officinale, 91, 92 Ocimum sanctum, 75, 86, 87, 98, 107, 109, 110,
nausea 112, 113, 114, 117, 118, 121, 124
AE alcuronium, 41 Ocimum suave, 98, 109, 110, 114
AE chemotherapy, 41 Ocimum tenuiflorum, 75, 86, 87, 98, 107, 109,
AE thiopental, 41 110, 112, 113, 114, 117, 118, 121, 124
AE vereuronium, 41 ocular hypertension, 15, 38
nausea & vomiting Oenothera biennis, 36, 106
AE chemotherapy, 62 ofloxacin, 107
AE cisplatin, 41 COPD exacerbation, 61
AE cyclophosphamide, 41 olanzapine, 106
nausea and vomiting schizophrenia, 45
AE doxorubicin, 41 olay, 9
Neem, 117 Olea europaea, 58, 106, 113
nellikka, 9 Oleo europaea, 118
neuropathic pain, 22 Olive, 58, 106, 113, 118
AE cisplatin, 26 omeprazole, 97, 103, 104, 105
AE vincristine, 20, 65, 75 Helicobacter pylori dyspepsia, 18
nevirapine, 18, 55, 93 omicha, 67
newborns, 14, 29, 46, 59 ondansetron, 106
175
nausea & vomiting, 42 pancreatic cancer, 18
Onion, 44, 85, 94, 98, 113 oxycodone, 105
open-angle glaucoma, 65 chronic pain, 22
opiate withrawal, 17 neuropathic pain, 22
opiates, 21, 107, 108 oxytetracycline, 123
chronic pain, 22 oxytetracylcine, 123
osteoarthritis, 70 Oyster mushroom, 100
opioid withdrawal paclitaxel, 68, 85, 93, 107, 112, 113, 114
AE morphine, 74 breast cancer, 79
opioids, 17 breast cancer cells, 9, 74
HIV neuropathic pain, 22 cancers, 69
neuropathic pain, 22 lung metastasis, 79
Opuntia ficus-indica, 63, 113 pain, 42
Opuntia spp., 63, 87, 109, 114 palo muneco, 64
oral contraceptives, 69 Panax ginseng, 12, 94, 99, 105, 108, 112, 114,
oral hypoglycemics, 14, 23, 29, 46, 59, 64, 87, 117
106, 107 Panax japonicus, 100
diabetes, 78 Panax notoginseng, 66, 88, 107, 112
diabetes type 2, 28, 32, 42 Panax quinquefolius, 7, 89, 98, 99, 105, 108,
oral mucositis 112, 114, 117
AE chemotherapy, 39 pancreatic cancer, 18
AE cisplatin, 26 pancreatic injury
AE cyclophopsphamide, 26 AE cyclosporine, 13
AE cytosine arabinoside, 26 pantoprazole, 103, 104
AE daunorubicin, 26 Papaya, 85
AE doxorubicin, 26 paracetamol, 24, 28, 39, 49, 110
AE fluorouracil, 26 AE hepatotoxicity, 52
AE L-asparginase, 26 paracetemol, 107
AE methotrexate, 26 osteoarthritis, 11, 70
AE radiotherapy, 26 paraplatin, 112
AE vincristine, 26 Parkinson's disease, 37
carboplatin, 79 Parsley, 91
chemotherapy, 79 Passiflora coerulea, 98
cisplatin, 79 Passiflora edulis, 86, 110
taxol, 79 Passiflora incarnata, 50, 61, 81, 86, 98, 107,
Orange, 84, 121 109
Oregano, 121, 122, 124 Passion flower, 50, 61, 81, 86, 98, 107, 109
Oregon grape, 58, 85, 92, 94, 96, 97, 99, 100, pau amarelo, 64
107, 109, 123, 124 Pau d’arco, 61
Origanum vulgare, 121, 122, 124 pau quassia, 64
osteoarthritis, 11, 20, 37, 38, 44, 70, 77 Paullinia cupana, 48, 106
osteoporosis Pausinystalia yohimbe, 81
AE dexamethasone, 45 Pelargonium, 61, 107
ototoxicity Pelargonium graveolens, 123, 124
AE gentamicin, 46 Pelargonium sidoides, 61, 107
ovarian cancer cells, 8 penformin, 75, 87
overactive bladder penicillin, 122
multiple sclerosis, 23 bacterial resistance, 48
oxacillin, 121, 122 Pennyroyal, 101
oxaliplatin, 105, 112 pentobarbital, 10, 54, 68, 75
colorectal cancer cells, 80 pentobarbitone, 61
176
Peppermint, 61, 86, 94, 99, 107, 109, 113, 117, polymyxin B, 122
123, 124 Pomegranate, 62, 94, 96, 109, 118, 121, 122,
Peppers, 26 124
perfloxacin, 106, 122 Pomelo, 94
E. coli, 29 Poria cocos, 50
peripheral neuropathy pravastatin, 86
AE cisplatin, 46 prednisolone, 106, 113
Persea americana, 89 AE oral mucositis, 39
Peruvian ginseng, 56 asthma, 17
pethidine, 105 prednisone, 107
neuropathic pain, 22 AE stomach ulcers, 54
Petroselinum sativum, 91 rheumatoid arthritis, 63, 66, 74
Peucedanum graveolens, 121 pregnancy, 16, 25, 27, 53, 64, 69, 70
Peucedanum praeruptorum, 90, 92 Prickly pear, 63, 87, 109, 113, 114
Peumus boldus, 19 prior to surgery, 41
P-glycoprotein, 84, 85 procarbazine, 107, 113
Pgp, 84 cancers, 69
Phellodendron amurense, 29 prolonged use, 21
phenacetin, 92 propoxyphene, 110
phenol sulfotransferases, 5, 99 propyphenazone, 110
phenprocoumon, 96 prostate cancer cells, 31, 63
phenylbutazone, 110 prulifloxacin, 107
phenylephrine, 7 chronic prostatitis, 66
phenytoin, 27, 84, 86, 90 Prunus armeniaca, 108
Phoradendron macrophyllum, 101 Prunus avium, 71, 107
Phyllanthus emblica, 9, 99 Prunus cerasus, 71, 107
Picrorhiza kurroa, 52, 106, 109, 110, 122 Prunus serotina, 120
Picrorrhiza kurroa, 120 Psyllium, 63, 87
Pimpinella anisum, 10 Pterocarpus marsupium, 87
Pinus maritima, 38 Pueraria lobata, 52, 94, 106, 109, 113
Pinus pinaster, 38, 106, 110, 113 Pueraria montana, 52
Piper longum, 55, 85, 94, 106, 117 Pueraria thomsonii, 100
Piper methysticum, 50, 91, 94, 114 Pueraria thunbergiana, 52, 106, 113
Piper nigrum, 18, 85, 94, 105, 108 Punica granatum, 62, 94, 96, 109, 118, 121,
pipericillin, 123 122, 124
piroxicam, 107, 110 Purple passion fruit, 86, 110
osteoarthritis, 70 pyrazinamide, 23, 105, 106, 107, 122, 123
Plantago afra, 63 AE hepatotoxicity, 10, 76, 78, 80
Plantago ispaghula, 63 AE immunosuppressant, 76, 80
Plantago lanceolata, 36, 106, 110 tubercular lymphadenitis, 40
Plantago ovata, 63, 87 tuberculosis, 11
Plantago psyllium, 63 Qian hu, 90, 92
Plasmodium berghei, 79 QR, 98
Plasmodium falciparum, 71, 79 Quassia, 64
Plasmodium yoelii, 52 Quassia (Surinam), 107, 109
Pleurotus ostreatus, 100 Quassia amara, 64, 107, 109
pneumococcal vaccine, 106, 124 quercetin, 85, 98, 113
pneumonia vaccine Rabdosia, 121
Streptococcus pneumoniae, 53 Rabdosia rubescens, 121
polycystic ovary syndrome, 56 rabeprazole, 103, 104
Polygonum multiflorum, 37, 99 radioiodine, 106, 107, 118
177
AE salivary gland damage, 76 Rubus chingii, 121
Graves' disease, 45 Rubus idaeus, 64, 109, 113
thyroid cancer, 45 Rubus occidentalis, 19, 91, 100, 108, 114, 118
radiotherapy Rubus occindentalis, 93, 98
AE oral mucositis, 26 Rubus spp., 91, 98, 100, 108
Rajgira, 117 ruda, 64
raloxifene, 112 Rugose rose, 121
breast cancer cells, 74 sacred basil, 75
raltegravir, 85 Safflower, 100
Raspberry, 64, 91, 98, 100, 109, 113 Saffron, 65, 100, 107, 109
Rattlebox, 83 Sage, 65, 107, 113, 121, 122
Red clover, 91, 94, 99, 100 salbutamol, 106
red wine, 99, 109 allergic asthma, 38
References, 126 mustard gas inhalation, 17
Reishi, 100, 113, 115, 118 salicylates, 110
renal colic, 35 salivary gland damage
reserpine AE radioidodine, 76
AE stomach ulcers, 73 Salmalia malabarica, 121
respiratory disorders, 33 salmeterol, 107
respiratory symptoms, 8 COPD, 61
Reynoutria multiflora, 37 Salvia miltiorrhiza, 32, 84, 92, 93, 94, 96, 97
Rhatany, 118 Salvia officinalis, 65, 107, 113, 121, 122
Rheum officinale, 27 Salvia sclarea, 120, 122
Rheum palmatum, 27, 84, 86, 120, 121 SAMA+SABA, 107
rheumatoid arthritis, 18, 32, 63, 66, 74, 78 COPD, 75
rhodamine, 85 sameterol, 106
Rhodiola, 109, 121 asthma, 38
Rhodiola crenuata, 107 Sampson root, 33
Rhodiola crenulata, 75 san qui ginseng, 66
Rhodiola rosea, 109, 121 Sanchi ginseng, 66, 88, 107, 112
rifampicin, 23, 105, 106, 107, 122, 123 Sanguinaria canadensis, 118
AE hepatotoxicity, 10, 53, 76, 78, 80 Santolina, 124
AE immunosuppressant, 76, 80 Santolina chamaecyparissus, 124
tubercular lymphadenitis, 40 Sappan, 122
tuberculosis, 11 saquinavir, 24, 39, 84, 93
rifampin, 122 Sarothamnus scoparius, 67
risperidone, 44 Sassafras, 83
ritonavir, 24, 35, 93, 94 Sassafras albidum, 83
rivastigmine, 105, 106 Satureja hortensis, 109
Alzheimer's disease, 13, 45 Saw palmetto, 66, 98, 101, 107
rofecoxib, 110 Schisandra, 67, 85, 94, 99, 110, 114
Roman chamomile, 64 Schisandra chinensis, 67, 85, 94, 99, 110, 114
Rosa canina, 32, 106 Schisandra sphenanthera, 68, 85, 86, 94, 113
Rosa rugosa, 121 schizophrenia, 21, 45, 81
Rose geranium, 124 Scotch broom, 67, 109
rose of China, 27 Scutellaria baicalensis, 27, 91, 109, 120
Rosemary, 65, 109, 123, 124 Sea buckthorn, 110, 117
rosiglitazone, 96 sedatives, 10
Rosmarinus officinalis, 65, 109, 123, 124 Senecio jabocaea, 83
rosuvastatin, 62, 84, 90, 113 Senecio vulgaris, 83
Royal sun agaricus, 87 Serenoa repens, 66, 98, 101, 107
178
sexual dysfunction diabetes type 2, 28
AE citalopram, 56 steatohepatitis
AE duloxetine, 56 AE ethanol, 20
AE escitalopram, 56 steroids, 106, 107
AE fluoxetine, 56, 65 rheumatoid arthritis, 32
AE fluvoxamine, 56 uveitis, 78
AE paroxetine, 56 sterol 27-hydroxylase, 90, 100
AE sertraline, 56 Stinging nettle, 70, 107, 110
AE SSRIs, 56 stomach damage
AE venlafaxine, 56 AE aspirin, 26
Shiitake, 67, 100, 107, 112 AE ethanol, 19, 40, 42
Shirazian thyme, 122 AE HCl, 19, 42
Shrubby basil, 98, 109, 110, 114 stomach ulceration
Silk tree, 68, 86 AE meloxicam, 76
Silybum marianum, 57, 84, 85, 87, 91, 94, 96, stomach ulcers
98, 106, 109, 110, 112, 113, 114, 117, AE acetic acid, 20, 76
118, 125 AE alcohol, 20
Simal, 121 AE aspirin, 73, 76
Simaruba, 64 AE cysteamine, 36
simvastatin, 25, 94, 105, 106, 107 AE ethanol, 18, 20, 26, 28, 49, 63, 73, 76
high cholesterol, 15, 30, 47, 60 AE ibuprofen, 54
sirolimus, 48, 93 AE indomethacin, 28, 36, 54, 73
skin damage, 24 AE NSAIDs, 54
smoking AE reserpine, 73
tobacco, 67 AE steroids, 54
SNRI, 106 Strawberry, 91, 98, 100, 109, 114
AE sexual dysfunction, 56 Streptococcus pneumoniae, 53
sodium valproate, 107 Sugar kelp, 88
migraine headache, 70 sulfasalazine, 107
Solanum nigrum, 120 ankylosing spondylitis, 74
sour cherry, 71 sulfazine, 107
Southern prickly ash, 121 rheumatoid arthritis, 63
Southern schisandra, 68, 86, 94 sulfonylureas, 7, 14, 23, 29, 36, 46, 59, 87
southern schizandra, 68 sulindac, 107
Sowa, 121 cancer chemoprevention, 72
Soy, 68, 85, 94, 99, 100, 107, 113, 114, 117, 118 osteoarthritis, 70
Spearmint, 61, 113 sulphacetamide, 122, 123
Spiny sowthistle, 125 SULT1A1, 5, 99
spironolactone Summer savory, 109
heart failure, 10 sunitinib, 84
SSRIs, 106 surgery, 41
AE sexual dysfunction, 56 Surinam quassia, 64
SSRI's, 11, 105 Surinam wood, 64
St. John’s wort, 69, 84, 94, 96, 109 S-warfarin, 97
St. John's wort, 17, 107, 117 Sweet annie, 71, 107
stable angina, 10 Sweet basil, 117
stanols, 105, 106, 107 Sweet cherries, 107
high cholesterol, 15, 30, 47, 60 Sweet cherry, 71
Star anise, 121, 123 Sweet clover, 98
statins, 106 Sweet tea, 121
congestive heart failure, 29 Swertia chirayita, 87
179
Symphytum officinale, 83 Clostridium tetani, 53
systemic inflammation, 78 tetracycline, 121, 122, 123
Syzygium aromaticum, 28, 98, 105, 109, 110, Teuchrium chamaedrys, 83
120, 122, 124 Thai chili, 26
Syzygium cumini, 87, 109, 117 Thea sinensis, 72
Szechuan lovage, 50 Theobroma cacao, 28, 88, 106, 118
Tabebuia avellanedae, 61 theophylline, 105
Tabebuia impetiginosa, 61 asthma, 17
tacrolimus, 19, 48, 68, 85, 93 thiopental
talinolol, 44, 57, 67, 77, 85 AE nausea, 41
tamoxifen, 85, 93, 94, 106, 112, 114 Thunder god vine, 74
breast cancer cells, 9, 73 Thunger god vine, 107
breast cancer survivors, 17 Thyme, 92, 121, 122, 123, 124
lung cancer cells, 73 Thymus broussonetii, 123
tamsulosin, 107 Thymus maroccanus, 123
benign prostatic hyperplasia, 66 Thymus spp., 92
Tanacetum parthenium, 101 Thymus vulgaris, 121, 122, 123, 124
Tansy ragwort, 83 thyroid cancer, 45
Tapinanthus sessilifolius, 85 Tibetan rhodiola, 75, 107
Tarragon, 83 ticlopidine, 94, 97
Tart cherry, 71, 107 tienchi ginseng, 66
Tassel hyacinth, 124 timolol, 107
taxol, 85, 107, 113, 114 glaucoma, 65
AE oral mucositis, 79 Tinospora cordifolia, 10, 78, 87, 117
colorectal cancer, 68 tizanidine, 105
Taxol, 9 multiple sclerosis, 23
taxotere, 105, 112 tobacco
breast cancer, 11 smoking, 67
Tea, 72, 84, 85, 91, 92, 94, 96, 97, 98, 100, 107, Tobacco, 54
109, 110, 112, 114, 118, 121, 122, 123, tobramycin, 123
124 tolbutamide, 12, 43, 62, 87, 96
Tea tree, 74, 107, 123, 124 Tomato, 113, 117
temozolamide, 107, 113 Tonka bean, 99
cancers, 69 topotecan, 107, 113, 115
temozolomide, 112 systemic inflammation, 78
Temu lawak, 113 torsemide, 104
tenoxicam, 107 toxic hepatitis, 81
osteoarthritis, 70 trabectedin, 27
Teratogens, 101 trabectidin, 106
Terminalia arjuna, 10, 105, 120 AE hepatotoxicity, 32
Terminalia belerica, 120, 121 Trachyspermum ammi, 108
Terminalia bellerica, 112 Trachyspermum copticum, 108
Terminalia bellirica, 108 Tragia involucrata, 87
Terminalia chebula, 120, 121, 122 tramadol, 105, 110
testicular toxicity neuropathic pain, 22
AE cyclophosphamide, 49 Trametes versicolor, 118
AE doxorubicin, 56 tricyclic antidepressants
testosterone, 17, 67, 91, 93, 99 HIV neuropathic pain, 22
testosterone and sperm reduction Trifolium pratense, 91, 94, 99, 100
AE nicotine, 70 Trigonella foenum-graecum, 36, 87, 91, 106,
tetanus vaccine, 106 109, 110
180
Tripterygium wilfordii, 74, 107 chemotherapy AE, 78
Tropical almond, 121 vincristine, 85, 105, 107, 110, 112, 113, 114
TS-1, 107 AE neuropathic pain, 20, 65, 75
GI cancer, 67 cancers, 69
tubercular lymphadenitis, 40 viral hepatitis, 81
tuberculosis Viranga, 121
ethambutol, 11 Vitamin B12, 103
isoniazid, 11 Vitamin C, 9, 103, 105, 114
pyrazinamide, 11 Vitamin D, 103
rifampicin, 11 Vitis spp., 118
tulasi, 75 Vitis vinifera, 88, 92, 94, 96, 97, 99, 109
Tulsi, 75, 86, 87, 98, 107, 109, 110, 112, 113, vomiting
114, 117, 118, 121, 124 AE chemotherapy, 21
tumor cells, 28 voriconazole, 97
Turkey tail, 96, 118 VRE
Turmeric, 26, 77, 85, 91, 92, 94, 96, 97, 98, 107, definition, 119
109, 110, 112, 113, 114, 115, 118, 121, warfarin, 7, 31, 32, 44, 49, 54, 55, 57, 88, 90
122 Watercress, 91, 92
Turnera diffusa, 99 weight loss
UDP-glucuronosyl transferases, 98 AE cisplatin, 34
UFT, 107 wewe gifi, 64
colorectal cancer, 68 White button mushroom, 99
GI cancer, 67 Wild ginger, 83
UGTs, 98 Wild yam, 81
Uncaria tomentosa, 24, 94, 105, 113, 117 Winter melon, 109
Urtica dioica, 70, 110 Withania somnifera, 11, 105, 108, 112, 114,
Urtica spp., 107 122, 124
Usnea, 121 withdrawal
Usnea spp., 121 AE benzodiazepines, 50, 61, 81
Uva ursi, 121 AE morphine, 12, 65, 70
uveitis, 78 Wormwood, 101
Vaccinium corymbosum, 91, 99, 100 xanthines, 107
Vaccinium macrocarpon, 31, 85, 91, 94, 96, 98, COPD, 75
106, 112, 113, 114, 117, 124 xerotic cheilitis
Vaccinium myrtillus, 15, 105, 122 AE isotretinoin, 36
Vaccinium spp., 84, 92, 94, 96, 97, 99 Yerba mansa, 101
Valerian, 50, 61, 81, 107, 109 Yohimbe, 81
Valerian officinalis, 50, 61 yohimbine, 81
Valeriana officinalis, 81, 107, 109 zafirlukast, 106
vancomycin, 122, 123 childhood asthma, 38
vasodilators Zanthoxylum clava-herculis, 121
heart failure, 10 Zataria multiflora, 122
vecuronium Zea mays, 31, 106, 112, 117
AE nausea, 41 zedoary, 94
venlafaxine, 106 zidovudine, 98
AE sexual dysfunction, 56 zinc, 85, 105, 106
verapamil, 85 mineral absorption, 19, 25, 27, 42, 55
Vernonia amygdalina, 85 Zingiber officinale, 40, 85, 88, 94, 99, 106, 109,
Vernonia cineraea, 98 110, 113, 118
Vernonia cinerea, 109 Ziziphus spinosa, 50
vinblastine, 107, 113
181
182

HCDI4 UPDATES AND ADDITIONS Dec' 16

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

HCDI4 UPDATES AND ADDITIONS Dec' 16

Uploaded by

Copyright:

Available Formats

UPDATES AND ADDITIONS

Last updated: December 6, 2016

KEYS TO INTERPRETING THE CONTENT IN THE BOOK AND AT THIS SITE

Abbreviations for the various modes of administration are used as follows:

ADDITIONAL INFORMATION IS AVAILABLE IN THESE UPDATES AND ADDITIONS FOR THE

B.7.1.d Influence on Constitutive Androstane Receptor (CAR)

C.1 During Pregnancy

BLACK CUMIN p.66

BLACK RASPBERRY NEW

CHINESE SKULLCAP p. 100

CORN SILK NEW

DOG ROSE p. 126

DONG QUAI p. 127

ECHINACEA ANGUSTIFOLIA p. 129

ECHINACEA PURPUREA p. 134

ENGLISH LAVENDER p. 141

EVENING PRIMROSE p. 148

FRENCH MARITIME PINE p. 158

HORSE CHESTNUT p. 204

OREGON GRAPE p. 254

PASSION FLOWER p. 258

PRICKLY PEAR p. 269

QUASSIA (SURINAM) p. 272

ROMAN CHAMOMILE p. 276

SANCHI GINSENG NEW

SAW PALMETTO p. 280

SCOTCH BROOM p. 282

SILK TREE p. 286

SOUTHERN SCHISANDRA NEW

ST. JOHN’S WORT p. 289

STINGING NETTLE p. 306

SWEET ANNIE p. 307

SWEET CHERRY NEW

TART CHERRY NEW

TEA TREE p. 317

THUNDER GOD VINE p. 318

TIBETAN RHODIOLA NEW

WILD YAM p. 334

A.8 Bioactivations of Phytochemical Procarcinogens and Potential Toxins ^

A.8.1 Bioactivations by Cytochrome P450 Isozymes (CYPs) and Sulfotransferases (STs) ^

B.1 Modifying Intestinal Absorption of Medicines and Phase III Metabolism

B.1.2 Enhancement of Absorption p. 368

B.1.2.c Enhanced Retention of Drugs by Inhibiting MRPs

B.1.3 No Influence on Drug Absorption in Humans

B.3 Potentiating Sedative or Tranquilizing Medicines p. 373

B.4 Modifying Blood Sugar In Diabetics p. 374

B.5 Modifying the Effects of Anticoagulants p. 379

B.7 Modifying Enzyme Activities in Metabolic Conversions p. 387

B.7.1.a Modulation by Phase I &/or Phase II &/or Phase III

Conversion/Clearance Inhibitors (Increase Bioavailability)

B.7.2.b Influence on CYP 2E1 Metabolic Conversion of Substrates

B.7.2.c Influence on CYP 3A Metabolic Conversion of Substrates

erythromycin − Gf,2590 sc2946

Procarcinogens: aflatoxin B1 − ep3201

B.7.2.d Influence on CYP 2C9 Metabolic Conversion of Substrates

B.7.2.e Influence on CYP 2C19 Metabolic Conversion of Substrates

B.7.2.f Influence on CYP 2D6 Metabolic Conversion of Substrates

B.7.3 Specific Enzyme Influences of Herbal Agents on Phase II Conjugation p. 426

B.7.3.f Influence on Activity of Estrogen Sulfotransferases (SULT1E1) NEW

B.7.4 Specific Enzyme Influences of Herbal Agents on Steroid Metabolism p. 433

C.2 While Breast Feeding

D.2 Drug and Vitamin Interactions with Mineral Supplements p. 467

E.1 Potentially Beneficial Combinations of Herbals with Drugs